Rozprawy doktorskie: „And Rat aorta rings”

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Ghalb, Faraa Amer Ahmed. "IN VITRO FUNCTIONAL INTERPLAY BETWEEN PERIVASCULAR ADIPOSE TISSUE AND FLAVONOIDS: CRITICAL ROLE OF BETA3 RECEPTOR AND SUPEROXIDE ANION." Doctoral thesis, Università di Siena, 2022. http://hdl.handle.net/11365/1207163.

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Flavonoids, a class of natural polyphenols abundantly present in our diet, have been shown to exert in vitro vasorelaxant activity. This was ascribed to a direct effect on the smooth muscle or factors released by the endothelium. Nowadays, perivascular adipose tissue (PVAT) is emerging as a fine regulator of blood vessel contractility. Therefore, it is conceivable to hypothesize that flavonoids vasoactivity may occur also through or is influenced, either positively or negatively, by PVATreleased factors. This hypothesis was assessed in vitro on rat aorta rings. Several flavonoids proved to display both antispasmodic and spasmolytic activity towards noradrenaline-induced contraction of rings deprived of PVAT (-PVAT). However, when PVAT was present (+PVAT), both activities of some flavonoids were lost and/or much decreased. In rings-PVAT, the superoxide donor pyrogallol mimicked the effect of PVAT, whereas in rings+PVAT the antioxidant mito-tempol restored both activities of the two most powerful flavonoids, namely apigenin and chrysin. The Rho-kinase inhibitor fasudil, or apigenin and chrysin concentration-dependently relaxed the vessel active tone induced by the Rho-kinase activator NaF; the presence of PVAT counteracted apigenin spasmolytic activity though only in the absence of mito-tempol. Similar results were obtained in rings pre-contracted with phenylephrine. Finally, when β3 receptors were blocked by SR59230A, the vasorelaxant activity of both flavonoids was no more affected by PVAT. These findings are coherent with the hypothesis that both noradrenaline and apigenin activated adipocyte β3 receptors with the ensuing release of mitochondrial superoxide anion, which once diffused toward myocytes counteracted flavonoid vasorelaxant activity, thus underlining the control of adipocytes upon the vascular tone. This phenomenon might limit the beneficial health effects of this class of natural compounds in patients affected by either obesity and/or other pathological conditions characterized by sympathetic nerve overactivity.

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Al-Zobaidy, Mohammed. "Differential actions of methlyarginines in the rat aorta." Thesis, University of Glasgow, 2012. http://theses.gla.ac.uk/3838/.

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The PhD project is about the Regulation of vascular tone by endothelium. It involves studying the effects of methylated arginine analogues such as monomethyl arginine (L-NMMA) and asymmetric dimethylarginine (ADMA) on nitric oxide (NO) activity in rat aorta using organ baths containing Krebs solution at 37 ˚C and gassed with 95% O2 and 5% CO2. These two inhibitors of endothelial nitric oxide synthase enzyme (eNOS) showed an anomalous action, as they inhibited basal NO activity (assessed by enhancement of phenylephrine-induced tone and by blocking relaxations produced by superoxide dismutase or the PDE5 inhibitor; T0156) but not that is stimulated by agonists like acetylcholine or the calcium ionophore A23187. After establishing these findings I will try to find the reason(s) for these paradoxical actions of these two endogenously synthesized inhibitors of eNOS.

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藍志洪 and Chi-hung Nam. "Effect of cerivastatin on endothelial function in rat aorta." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2001. http://hub.hku.hk/bib/B42575837.

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Nam, Chi-hung. "Effect of cerivastatin on endothelial function in rat aorta." Click to view the E-thesis via HKUTO, 2001. http://sunzi.lib.hku.hk/hkuto/record/B42575837.

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Vinh, Vu Huu. "Comparative contractile effects of halothane and sevoflurane in rat aorta." Kyoto University, 2001. http://hdl.handle.net/2433/150545.

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Gorp, Adrianus Wilhelmus van. "The relationship between structural and in vivo dynamic mechanical properties of the thoracic aorta in rats influence of ageing and hypertension /." Maastricht : Maastricht : Universiteit Maastricht ; University Library, Maastricht University [Host], 1999. http://arno.unimaas.nl/show.cgi?fid=7537.

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Rice, Kevin M. "Effects of aging on pressure-induced MAPK activation in the rat aorta." Huntington, WV : [Marshall University Libraries], 2005. http://www.marshall.edu/etd/descript.asp?ref=526.

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管漢偉 and Hon-wai Michael Koon. "Potentiating effects of platelet activating factor on endothelin-1 induced rat arota vasoconstriction." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1998. http://hub.hku.hk/bib/B31221014.

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Koon, Hon-wai Michael. "Potentiating effects of platelet activating factor on endothelin-1 induced rat arota vasoconstriction /." Hong Kong : University of Hong Kong, 1998. http://sunzi.lib.hku.hk/hkuto/record.jsp?B20565689.

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Ferreira, Iolanda João Mora Cruz de Freitas. "Pre and postjunctional effects of rosiglitazone on the isolated rat aorta and heart." Master's thesis, Faculdade de Medicina da Universidade do Porto, 2010. http://hdl.handle.net/10216/61097.

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Ferreira, Iolanda João Mora Cruz de Freitas. "Pre and postjunctional effects of rosiglitazone on the isolated rat aorta and heart." Dissertação, Faculdade de Medicina da Universidade do Porto, 2010. http://hdl.handle.net/10216/61097.

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Li, Min. "Constrictor prostanoid-potentiated vascular contraction: regulation of endothelial and vascular smooth muscle mechanism by estrogen." Diss., Texas A&M University, 2004. http://hdl.handle.net/1969.1/549.

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The objectives of this research were to elucidate the involvement of constrictor prostanoids in the vascular reactivity to vasopressin (VP) and the role of estrogen in the regulation of the constrictor prostanoid mechanism in the female rat. Aortas obtained from male, intact (InT)-, ovariectomized (OvX)- and OvX + estrogen-replaced (OvX+Est)-female rats were studied. Contractile responses to VP were examined in the presence of nonselective and selective cyclooxygenase (COX) inhibitors. Basal and VP-stimulated release of thromboxane A2 (TxA2) and prostacyclin (PGI2) from the aortic wall were measured. Concentration-response curves to exogenous TxA2 were also obtained. To elucidate the regulatory effects of estrogen on the constrictor prostanoid pathway, the expression of COX-1, COX-2, thromboxane synthase (TxS) and thromboxane receptor (TP) mRNA were detected by reverse transcription-polymerase chain reaction (RT-PCR). Further, immunohistochemistry was employed to determine COX-1, COX-2 and TxS protein expression in aortic endothelium and vascular smooth muscle. The major findings of this research are that: 1) The contractile responses of the female rat aorta to VP were enhanced by COX-2-mediated production of constrictor prostanoids (PGH2/TxA2), and this mechanism is potentiated by estrogen; 2) Vascular reactivity to exogenous TxA2 was higher in the female than in the male rat aorta, and OvX attenuated and estrogen replacement therapy restored vascular reactivity to TxA2 in the female aorta; 3) VP-stimulated release of endogenous TxA2 and PGI2 were higher in the female than in the male rat aorta, and OvX attenuated and estrogen replacement therapy restored VP-stimulated release of these endogenous prostanoids by the female aorta; and 4) The expression of COX-2 and TxS mRNA and protein, and the expression of TP mRNA were higher in InT-female than in male, and were reduced by OvX and restored by estrogen replacement therapy. In conclusion, estrogen potentiated contractile responses of the female rat aorta to VP by upregulating the expression of COX-2, TxS and TP; thereby enhancing VP-induced release of TxA2, as well as the vascular reactivity to endogenous TxA2.

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Manio, Michael Magtoto. "In vivo exposure to lipopolysaccharide unmasks contractions to the alpha2-adrenergic agonist dexmedetomidine in the rat aorta." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/208015.

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Dexmedetomidine is α2-adrenergic agent and commonly used in the intensive care setting. It is used primarily to sedate critically ill patients in various surgical, endoscopic and radiologic procedures. This medication gained superiority with other sedatives with a distinct advantage of less depression of the respiratory system. Although dexmedetomidine is often administered to septic patients, the vascular effect has not been fully studied in this clinical setting. In this thesis, rats were administered saline or bacterial lipopolysaccharide (LPS) 1, 10 and 20 mg/kg. Aortic rings were obtained after two, 24 and 72 hours exposure and dexmedetomidine-induced contractions were investigated. Rats could not tolerate prolonged exposure to 20 mg/kg LPS and died during the process. Systolic, diastolic and mean arterial pressures were reduced after LPS exposure while heart rates were elevated. Body temperatures were elevated after LPS administration (all doses and time), except a reduction at two hours with 1 mg/kg LPS. LPS increased the plasma levels of tissue necrosis factor-α and interleukin-6 after two hours LPS administration but not at 24 and 72 hours. In aortic rings with functional endothelium from rats with or without LPS exposure, dexmedetomidine had no effect on resting tension. Dexmedetomidine produced concentration-dependent contractions (10 nM to 10 μμM) after incubation with endothelial nitric oxide synthase (NOS) inhibitor L-NAME or removal of endothelium in rings without and with exposure to LPS for two, 24, 72 hours. LPS administration dose-dependently attenuated dexmedetomidine-induced contractions. In the presence of 1400W (inducible NOS inhibitor) the contractile response to dexmedetomidine was potentiated suggesting a role of NO produced by iNOS. Treatment with MnTMPyP attenuated dexmedetomidine-induced contractions indicating that the superoxide dismutase mimetic might increase NO availability by reducing superoxide. A significant role of iNOS was further supported by the detection of iNOS expression in aortic rings after LPS exposure at two, 24, and 72 hours when compared to non-LPS exposed group. Use of selective α2A and α2B receptor antagonists (BRL44408 and ARC239 respectively) showed that dexmedetomidine-induced contractions were mediated mostly via α2A receptor subtype as the former but not the latter agent significantly reduced contractions. Serotonin (5-HT, 10 nM to 100 μμM) and phenylephrine (1 nM to 100 μμM) produced concentration-dependent contractions in aortic rings with and without LPS exposure. The maximal responses to 5-HT and phenylephrine were increased at 10 mg/kg LPS as compared to a reduction in contractions by dexmedetomidine with LPS exposure at 1 and 10 mg/kg supporting alterations in α2 receptors occurred after LPS administration. In conclusion, the present study demonstrated that the vascular contractile responses of dexmedetomidine in the absence of endothelium or in the presence of eNOS inhibition were reduced in the presence of LPS at different time points and at different doses in aortic rings while two other receptor mediated vasoconstrictors, 5-HT and phenylephrine were affected. Our findings suggest that LPS may preferentially reduce the vascular contractile responses of dexmedetomidine and it is essential to exercise caution when the drug is administered to critically ill patients or with endothelial dysfunction. published_or_final_version Pharmacology and Pharmacy Doctoral Doctor of Philosophy

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Taylor, S. G. "The modulatory role of the vascular endothelium on spasmogenic and relaxant responses in rat aorta." Thesis, University of Manchester, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.378822.

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Qu, Chen, and 屈晨. "Modulation of endothelium-dependent contractions by chronic inhibitionof nitric oxide synthase in the rat aorta." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B41290835.

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Little, Marie-Térèse E. "The ontogeny of acyl coenzyme A: cholesterol acyltransferase in rat liver, intestine, adipose tissue, and aorta." Thesis, University of British Columbia, 1990. http://hdl.handle.net/2429/29416.

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Epidemiological studies have shown that cholesterol is a major risk factor for the development of atherosclerosis. Since the atherosclerotic plaque develops over a long period interventions early in life may be of some benefit. In addition, it has been shown that the enzymes involved in cholesterol metabolism can be manipulated in early life. Therefore, studies of the developmental patterns of the key enzymes in cholesterol metabolism are of great importance. Acyl coenzyme A: cholesterol acyltransferase (ACAT) is the primary enzyme which catalyzes the conversion of free cholesterol to cholesterol esters in cells. A better understanding of the role and control of ACAT during development is needed in order to trace the possible causes in early life that lead to atherosclerosis in the adult. This research focused on the developmental pattern of ACAT in the rat liver, intestine, brown and white adipose tissue (BAT and WAT, respectively) and aorta. Age specific changes were observed in the rat liver, intestine and BAT. The rat liver and intestine possess significant amounts of ACAT activity throughout development and there appears to be marked variations in activity during this time. The rat BAT and WAT appear to be devoid of ACAT activity throughout development with the exception of adult BAT. Due to the small amount of the aortic tissue samples and/or the insensitivity of the assay, no definite conclusions could be made from this aortic study. In searching for factors that might control the ACAT enzyme the immediate effects of short-term manipulation of diet on the activity of ACAT were studied. The rats were all weaned early on day 18 to one of the following diets: Purina Rat Chow, high carbohydrate (HG) , high fat (HF) , or 2% cholesterol. The HF was the only diet that consistently increased hepatic ACAT activity in all the age groups. The cholesterol diets significantly increased the activity of ACAT in the 22 and 25 day old rats. The HG diet increased the activity of ACAT in the 22, 25, and 30 day old rats. No significant differences were observed between the adult control and HG diet groups. Feeding rats a HF or HG diet precipitated a dramatic drop in intestinal ACAT activity in the 22 day old animals. These effects were not observed in the older animals. The high cholesterol diet had no significant effect on the intestinal enzyme's activity in 22 day old rats. There was no significant change in the BAT and WAT ACAT activity with the experimental diets with the exception that all the experimental diets decreased ACAT activity in the adult BAT. Medicine, Faculty of Medicine, Department of Experimental Medicine, Division of Graduate

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Hussain, Monira Begum. "Characterisation of the #alpha#â†1-adrenoceptor subtypes in rat isolated aorta, mesenteric and pulmonary arteries." Thesis, University College London (University of London), 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.286507.

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Qu, Chen. "Modulation of endothelium-dependent contractions by chronic inhibition of nitric oxide synthase in the rat aorta." Click to view the E-thesis via HKUTO, 2008. http://sunzi.lib.hku.hk/hkuto/record/B41290835.

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Qu, Chen, та 屈晨. "The dual peroxisome proliferator-activated receptor α/[gamma] agonist Wy14643 improves endothelial function in the aorta of thespontaneously hypertensive rat". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B46917561.

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Furutani, Hidekatsu. "Ca[2+] entry channels involved in contractions of rat aorta induced by endothelin-1, noradrenaline and vasopressin." Kyoto University, 2003. http://hdl.handle.net/2433/148772.

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Otto, Anne. "The protection of rosuvastatin and ramipril against the development of nitrate tolerance in the rat and mouse aorta." Doctoral thesis, Universite Libre de Bruxelles, 2006. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/210861.

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Organic nitrates, such as nitroglycerine (NTG), are widely used for their potent vasodilator capacity in the management of coronary artery disease and heart failure. Unfortunately, their beneficial effect is rapidly lost due to the development of nitrate tolerance, which is translated by an impaired vasorelaxation to NTG and an increased oxidative stress production. Although the mechanisms of the development of nitrate tolerance are still not fully elucidated, much interest has been focused in treating nitrate-receiving patients together with other drugs in order to overcome the development of nitrate tolerance. The Nitric Oxide generating enzyme, eNOS, and the superoxide anion generating enzyme, NAD(P)H oxidase, have been suggested to play a role in the development of nitrate tolerance. The aim of this study was to analyse the underlying mechanism by which ramipril, an ACE inhibitor and rosuvastatin, a new molecule of the statin class, are able to protect against the development of nitrate tolerance in the aortas isolated from rats, wild-type (wt) and eNOS-/- mice. These results show that ramipril as well as rosuvastatin are able to protect against the development of nitrate tolerance in the wt and eNOS-/- mice aortas suggesting that eNOS is not necessary for their protective effect. The aortas from nitrate tolerant rats and mice showed a significant increase in the NAD(P)H oxidase activation compared to the aortas from the control and from the co-treated ramipril+NTG or rosuvastatin+NTG animals. In line with these findings were the results obtained by RT-PCR analysis: the mRNA expression of the different subunits of the NAD(P)H oxidase, such as gp91phox, p22phox, were significantly decreased after rosuvastatin or ramipril treatment in wt and eNOS-/- mice aortas. Apocynin, the NAD(P)H oxidase inhibitor was also able to inhibit the development of nitrate tolerance in the rat and mouse aortas. In conclusion, these results suggest that rosuvastatin and ramipril are able to protect against the development of nitrate tolerance by counteracting the nitrate-induced oxidative stress. The mechanism of protection involves a direct interaction with the NAD(P)H oxidase pathway and seems to be completely independent of the eNOS pathway. Doctorat en sciences pharmaceutiques info:eu-repo/semantics/nonPublished

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Chrétien, Marc Laurent. "Potentiation of carbon monoxide-induced relaxation of rat aorta by YC-1 (3-(5'-hydroxymethyl-2'furyl)-1-benzylindazole)." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp05/MQ63282.pdf.

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Brawley, Lee. "Classical and atypical β-andrenoceptor subtypes mediating relaxation in rat isolated aorta : role of the endothelium/nitric oxide pathway". Thesis, Glasgow Caledonian University, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.313178.

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Baltzer, Wendy Irene. "The role of constrictor prostanoids in the development of aortic coarctation-induced hypertension in male and female rats." Diss., Texas A&M University, 2003. http://hdl.handle.net/1969.1/1525.

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Vascular reactivity to vasopressin and phenylephrine is potentiated by constrictor prostanoids (CP) in normotensive female (F) but not male (M) rat aorta and CP function is estrogen-dependent. This study investigated the effects of estrogen on CP function and arterial blood pressure (MAP) during development of aortic coarctation-induced hypertension (HT). M and F rats, (15-18 wks.) in four groups: normotensive (NT), hypertensive (HT), ovariectomized (OVX), and OVX estrogen-replaced (OE), underwent abdominal aortic coarctation or sham surgery (NT). At 14 days, SQ 29,548 (SQ, Thromboxane A2 (TXA2) receptor antagonist) was given i.v. to the groups. In another experiment, rats received Ridogrel (TXA2 receptor antagonist+TXA2 synthase (TXS) inhibitor) or vehicle (methyl cellulose) daily, for 14 days. Thoracic aortae were analyzed for morphology, incubated in Krebs Henseleit Buffer (KHB) ± angiotensin II (ANG II), or underwent continuous pulsatile flow and pressure experiments (PFP) with KHB ± ANG II. Perfusate was analyzed for thromboxane B2 (TXB2) and prostaglandin F1α (PGF1α). RT-PCR and immunohistochemistry were performed for TXS. MAP was higher in F-HT than in M-HT after 14 days. SQ infusion reduced MAP substantially more in F-HT and OE-HT than in others. Ridogrel prevented increases in MAP in F/OE-HT rats, but not M/OVX-HT. Basal release of TXB2 and PGF1α increased to a greater extent in F-HT than in M-HT relative to their controls. ANG II-stimulated TXB2 and PGF1α release increased to a greater extent in F-HT than in M-HT. With or without ANG II, TXB2 production in HT during PFP increased with estrogen. PGF1α increased during PFP with estrogen, however not with ANG II. Pressurization resulted in less diameter change in F and OE-HT than in OVX-HT. Elastin increased with HT (inhibited by Ridogrel) in all but M. Collagen increased in HT with estrogen (inhibited by Ridogrel). Neither OVX-HT nor Ridogrel had any effect on morphology. Estrogen increased TXS with HT. Estrogen enhanced vascular CP and MAP in F-HT by increased expression of TXS and collagen density in the vasculature indicating that in aortic coarctation-induced HT, CP are upregulated by estrogen. Specific forms of HT in human beings may involve estrogen-induced vascular CP upregulation.

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MagalhÃes, Pedro Jorge Caldas. "Estudo farmacologico do Ãleo essencial do Croton nepetaefolius Baill sobre os musculos lisos traqueal e vascular e sobre as propriedades eletrofisiologicas de neuronios fasicos de ganglio celiaco." Universidade Federal do CearÃ, 2002. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=50.

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FundaÃÃo Cearense de Apoio ao Desenvolvimento Cientifico e TecnolÃgico CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior Estudo farmacolÃgico do Ãleo essencial de Croton nepetaefolius Baill. sobre o mÃsculo liso traqueal e vascular e sobre as propriedades eletrofisiolÃgicas de neurÃnios fÃsicos de gÃnglio celÃaco. Pedro Jorge Caldas MagalhÃes, Tese de Doutorado em Farmacologia, UFC, 2002. Croton nepetaefolius Baill Ã um arbusto aromÃtico do Nordeste brasileiro, conhecido como âmarmeleiro sabiÃâ, utilizado na medicina popular como antiespasmÃdico e carminativo. Os principais constituintes do seu Ãleo essencial sÃo 1,8-cineol, metil-eugenol, xantoxilina e terpineol. Recentemente, demonstraram-se propriedades antiespasmÃdica intestinal, hipotensiva, antiinflamatÃria e analgÃsica para o Ãleo essencial do Croton nepetaefolius (OECN). Neste trabalho, caracterizamos os efeitos farmacolÃgicos do OECN sobre o mÃsculo liso respiratÃrio e vascular de rato e cobaio e sobre o funcionamento elÃtrico de neurÃnios de gÃnglio celÃaco de cobaio. Usamos preparaÃÃes in vitro de vasos sanguÃneos de ratos e cobaios machos (aorta e vasos mesentÃricos) e anÃis de traquÃia, mantidos em soluÃÃo nutridora, aerada, pH 7,4, a 37 oC, para registro isomÃtrico das contraÃÃes musculares. Usamos tambÃm gÃnglios celÃacos intactos de cobaios, mantidos em temperatura ambiente in vitro, para os registros eletrofisiolÃgicos pela tÃcnica do microeletrodo intracelular. In vivo, avaliamos as aÃÃes do OECN sobre a pressÃo arterial mÃdia e alguns parÃmetros cardÃacos, respiratÃrios e hematolÃgicos em ratos. O OECN (0,1 - 1000 microgrma/ml) relaxou o tÃnus basal (5 mM [K+]) e o tÃnus aumentado por K+ (60 mM) em traquÃia de cobaio, de maneira dependente de concentraÃÃo (CE50 de 4 e 63 micrograma/ml, respectivamente). Em tecidos de cobaios previamente sensibilizados, o OECN (300 e 600 micrograma/ml), reduziu a contraÃÃo induzida pela apresentaÃÃo do antÃgeno sensibilizante (ovalbumina). Na faixa de concentraÃÃo de 100 a 400 micrograma/ml, bloqueou as contraÃÃes induzidas por histamina e PGF2 alfa. O OECN inibiu as contraÃÃes induzidas por histamina, carbacol e KCl com CI50 na faixa de 100 - 130 micrograma/ml. Em aorta de rato e cobaio, relaxou a contraÃÃo induzida por 60 mM de K+ (CI50 de 32 e 200 micrograma/ml, respectivamente). Em rato, mas nÃo em cobaio, este relaxamento foi parcialmente inibido pela retirada do endotÃlio vascular ou pela adiÃÃo de 100 micrograma M de L-NAME. Em aorta de cobaio, o OECN inibiu as contraÃÃes independentes de Ca2+, induzidas por dibutirato de forbol e por K+ hiperosmolar na soluÃÃo nutridora. O OECN diminuiu preferencialmente a pressÃo arterial em ratos DOCA-sal do que em ratos nefrectomizados e, bloqueou mais potentemente as contraÃÃes induzidas pela fenilefrina em aorta de rato DOCA do que dos animais nefrectomizados. O OECN, metil-eugenol e terpineol, aumentam o fluxo de lÃquido pela circulaÃÃo mesentÃrica de rato, sendo este efeito parcialmente inibido pela presenÃa de L-NAME. Em nenhuma dessas preparaÃÃes o OECN produziu hiperpolarizaÃÃo do potencial transmembrana. Em neurÃnios fÃsicos de gÃnglio celÃaco de cobaio, o OECN diminuiu significativamente o aumento da excitabilidade produzido pela histamina sem alterar as propriedades passivas e ativas dos neurÃnios. Em conclusÃo, o OECN relaxa o mÃsculo liso das vias aÃreas, Ã um agente hipotensor e vasorelaxante e diminui a excitabilidade induzida por histamina em neurÃnios autonÃmicos. Seus efeitos sÃo, provavelmente, intracelulares ou mediados por proteÃna quinase C. Croton nepetaefolius is an aromatic bush found in brazilian Northeast region, called âmarmeleiro sabiÃâ, and it is used in folk medicine as an antispasmodic and carminative agent. Its essential oil is comprised of 1,8-cineole, methyl-eugenol, xanthoxylin, terpineol and others constituents. Recent studies showed some pharmacological activities of the essential oil of Croton nepetaefolius (EOCN) as an intestinal antispasmodic, hypotensive, anti-inflammatory and analgesic agent. Our aim in this work was to evaluate the effects of EOCN on airway and vascular smooth muscle and also on autonomic neurons. We used in vitro models of rat and guinea-pig isolated vessels and guinea-pig tracheal rings for isometric recording of the smooth muscle contractions. Guinea-pig celiac ganglion, was used for intracellular microelectrode recording of electricophysiological signals. Moreover, mean arterial pressure, cardiovascular, respiratory and hematologic parameters were measured in vivo in rats. EOCN (0,1 â 1000 microgram/ml) relaxed basal and K+-increased guinea-pig tracheal tonus (EC50 = 4 and 63 microgram/ml, respectively), in a concentratation-dependent manner. In ovalbumin-sensitized guinea-pig tissues, EOCN inhibited the antigen-induced contraction. EOCN (100 - 400 microgram/ml) blocked the histamine- and PGF2alpha -induced contractions. The contractions induced by histamine, carbacol and KCl were inhibited by EOCN with IC50s between 100-130 microgram/ml. In rat and guinea-pig aortic rings, EOCN relaxed the 60 mM K+-induced contractions (IC50 = 32 and 200 microgram/ml, respectively). Only in rat tissues, this EOCN-induced relaxation was partially inhibited by both L-NAME (100 microgram M) or endothelium lack. In guinea-pig aortic rings, EOCN inhibited the Ca2+-independent phorbol esther- and hyperosmotic K+- induced contractions. EOCN, preferably, diminished the mean arterial pressure and inhibited the aortic rings phenylephrine-induced contractions in DOCA-salt treated rats rather than uninephrectomized rats. Both EOCN, methyl-eugenol and terpineol increased the flow through rat mesenteric bed. This effect was partially blocked by L-NAME (50 microgram M). EOCN did not produce hyperpolarization of the transmembrane potential. In celiac ganglion phasic neurons, EOCN signicantly inhibited the histamine-induced increase of the neuronal excitability. In conclusion, EOCN is an airway smooth muscle relaxant, hypotensor and vasorelaxant agent, and it is a blocker of the stimulant histamine activity on autonomic neurons. Its effects are, probably, mediated by an intracellular action or protein C kinase modulation.

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Zhang, Xiao-feng. "Pharmacological Characterization of Ca^<2+> entry channels in ET-1-induced contraction in rat aorta using LOE 908 and SK&F 96365." Kyoto University, 1999. http://hdl.handle.net/2433/181252.

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Olah, Mark E. "Effects of calcium channel blockade and intracellular calcium antagonism on endothelium-dependent responses of the isolated rat aorta and influence of the endothelium on drug action /." The Ohio State University, 1988. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487590702989006.

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Monteiro, Fábio de Souza. "Ação relaxante da fração de alcaloides totais obtida de Solanum paludosum Moric. envolve modulação positiva da via do óxido nítrico e dos canais de K+ em íleo de cobaia e aorta de rato." Universidade Federal da Paraíba, 2013. http://tede.biblioteca.ufpb.br:8080/handle/tede/6772.

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Made available in DSpace on 2015-05-14T12:59:47Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 2456836 bytes, checksum: 09d3f72dc7985812ae8e5dab865bed8c (MD5) Previous issue date: 2013-02-19 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES Solanum paludosum Moric. (Solanaceae), popularly known as "jurubeba roxa" in Brazil Northeast, is used as a substitute for Solanum paniculatum ( jurubeba-verdadeira ) in folk medicine to treat hypertension and gastrointestinal disorder. In previous studies performed by Monteiro (2009) with total alkaloid fraction obtained from the root bark of this species (FAT-SP) was shown that its presented spasmolytic activity on smooth muscle, being more potent on guinea pig ileum and rat aorta. On guinea pig ileum, the relaxing effect involved antimuscarinic activity, and on rat aorta the NO/GC pathways. As the fraction has constituted by glycoalkaloids and many are known to exhibit cytotoxic activity, this activity was assessed in longitudinal layer myocytes from guinea pig ileum. In this work, we found that FAT-SP has no cytotoxic activity in these cells even the highest concentration tested (750 μg/mL), then we proceeded with the investigation of the relaxant action mechanism of FAT-SP on guinea pig ileum and rat aorta until that concentration. FAT-SP showed a relaxant effect on guinea pig ileum resistant simultaneous blockade of cholinergic and adrenergic pathways with guanethidine and atropine, respectively, suggesting there is involvement of NANC pathway; L-NAME (NOS competitive inhibitor) reduced FAT-SP relaxing potency, which was reversed in the presence of L-arginine, the substrate for NOS, suggesting that NO may be via NANC neurotransmitter. However, no reduction of the relaxing potency in the presence of ODQ, selective inhibitor of GC soluble, suggesting no participation of the GC in the FAT-SP relaxant action mechanism on guinea pig ileum. In the other hand, K+ channels participation (BKCa and SKCa) was evidenced by FAT-SP relaxing potency reduction on CsCl 5 mM presence (K+ channels nonselective blocker), TEA+ 1 mM (BKCa selective blocker) or apamin 100 nM (SKCa selective blocker). On rat aorta, it was observed participation pathway NO/cGMP/PKG, as can be evidenced by FAT-SP relaxing potency reduction in L-NAME 3 x 10-4 or 10-4 M presence and by inhibitory effect reversibility in L-arginine presence, as well as relaxing potency reduction in Rp-8-Br-cGMP 3 x 10-5 M presence, PKG selective inhibitor. Also, it was shown endothelial calmodulin participation because FAT-SP relaxing potency was reduced in presence calmidazolium 10-5 M, endothelial calmodulin selective inhibitor. The channel K+ participation (KV, SKCa and KATP) was evidenced by experiments with TEA+ 10 mM (K+ channels nonselective blocker), 4-AP 1 mM (KV selective blocker), apamin 5 x 10-8 M, glibenclamide 10-5 M (KATP selective blocker). Further, was showed partial inhibition of Ca2+ mobilization induced by IP3 of RS, but not by caffeine (20 mM). Thus, FAT-SP relaxing effect involves NO, BKCa and SKCa participation, on guinea pig ileum and endothelial calmodulin, NO/cGMP/PKG pathway and K+ channels (KV, SKCa and KATP) on rat aorta. Solanum paludosum Moric. (Solanaceae), conhecida popularmente como jurubeba-roxa no Nordeste do Brasil, é utilizada como sucedânea de Solanum paniculatum ( jurubeba-verdadeira ) na medicina popular para tratamento de hipertensão e desordem gastrintestinal. Estudos anteriores, realizados por Monteiro (2009) com a fração de alcaloides totais obtida da casca da raiz desta espécie (FAT-SP) demonstraram que a mesma apresentou atividade espasmolítica em músculos lisos, sendo mais potente em íleo de cobaia e aorta de rato. Em íleo de cobaia, o efeito relaxante envolve atividade antimuscarínica e, em aorta de rato, a participação da via NO/GC. Como a fração possui na sua composição glicoalcaloides e muitos destes são conhecidos por apresentar atividade citotóxica, avaliou-se esta atividade em miócitos da camada longitudinal do íleo de cobaia. Neste trabalho, observou-se que a FAT-SP não apresenta atividade citotóxica nessas células na concentração máxima testada (750 μg/mL), portanto prosseguiu-se com a investigação do mecanismo de ação relaxante da FAT-SP em íleo de cobaia e aorta de rato até essa concentração. A FAT-SP apresentou um efeito relaxante em íleo de cobaia resistente ao bloqueio simultâneo das vias adrenérgica e colinérgica com guanetidina e atropina, respectivamente, sugerindo-se que há a participação da via NANC; o L-NAME (inibidor competitivo da NOS), reduziu a potência relaxante da FAT-SP, que foi revertida na presença da L-arginina, substrato para a NOS, sugerindo que o neurotransmissor da via NANC pode ser o NO. Porém, não houve redução da potência relaxante na presença de ODQ, inibidor seletivo da GC solúvel, o que sugere a não participação da GC no mecanismo de ação relaxante da FAT-SP em íleo de cobaia. Por outro lado, a participação dos canais de K+ (BKCa e SKCa) foi evidenciada pela redução da potência relaxante da FAT-SP na presença de 5 mM de CsCl (bloqueador não seletivo dos canais de K+), de 1 mM de TEA+ (bloqueador seletivo dos BKCa) ou 100 nM de apamina (bloqueador seletivo dos SKCa). Em aorta de rato, observou-se que há a participação da via NO/GMPc/PKG, como evidenciado pela redução da potência relaxante da FAT-SP na presença de 10-4 ou 3 x 10-4 M de L-NAME, e da reversibilidade do efeito inibidor na presença da L-arginina, bem como, da redução da potência relaxante na presença de 3 x 10-5 M de Rp-8-Br-cGMPS, inibidor seletivo da PKG. Ademais, foi demonstrado que há a participação da calmodulina endotelial, pois houve redução da potência relaxante da FAT-SP na presença de 10-5 M de calmidazolium, inibidor seletivo da calmodulina endotelial; participação dos canais de K+ (KV, SKCa e KATP) evidenciado pelos experimentos com 10 mM de TEA+ (bloqueador não seletivo dos canais de K+), 1 mM de 4-AP (bloqueador seletivo dos KV), 5 x 10-8 M de apamina e 10-5 M de glibenclamida (bloqueador seletivo dos KATP). Observou-se ainda a inibição parcial da mobilização do Ca2+ do RS induzida pelo IP3, mas não por cafeína (20 mM). Assim, o efeito relaxante da FAT-SP envolve a participação do NO e dos BKCa e SKCa em íleo de cobaia, e da calmodulina endotelial, bem como da via NO/GMPc/PKG e canais de K+ (KV, SKCa e KATP) em aorta de rato.

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Medeiros, Marcos Antônio Alves de. "Investigação do efeito vasorelaxante e caracterização eletrofisiológica dos alcalóides curina e reticulina." Universidade Federal da Paraíba, 2009. http://tede.biblioteca.ufpb.br:8080/handle/tede/6829.

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Made available in DSpace on 2015-05-14T13:00:06Z (GMT). No. of bitstreams: 1 parte1.pdf: 1450137 bytes, checksum: 1838bf2efddf0ca147f276df88417bb6 (MD5) Previous issue date: 2009-09-24 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES It was been demonstrated that curine and reticuline, induced a vasodilator effect in the rat small mesenteric arteries through inhibition of voltage-gated Ca2+ channels (VGCC). These compounds, curine and reticuline were isolated from the root barks of Chondrondendron platyphyllum and Ocotea duckei Vattimo, respectively, therefore the aim of this work was to evaluate the vasodilator mechanism of curine and reticuline, bisbenzylisoquinoline alkaloids (BBA), isolated from the root barks of Chondrondendron platyphyllum and Ocotea duckei Vattimo, respectively, using functional and molecular approaches. Tension measurements in aorta rings, whole-cell patch-clamp and confocal techniques were employed to study the action of these alkaloids. The A7r5 smooth muscle derived cell line was used for Ca2+ currents measuring and the intracellular calcium concentration ([Ca2+]i) were evaluated using confocal microscopy. The main results are as follows: in aortic rings, curine (3 - 300 μM) antagonized KCl (60 mM) and Bay K8644 (3 x 10-7 M) induced contractions. In whole-cell configuration, curine reduced the voltage-activated peak amplitude of ICa,L in a concentration-dependent manner. However, the Ca+2 current density versus voltage relationship and maximal activation voltage of ICa,L were not changed. Moreover curine did not also affect the steady-state activation of ICa,L, but shifted the steady-state inactivation curve of ICa,L for more negative potentials, however this effect was not changed in the presence of IBMX, dbcAMP and 8-brcGMP, suggesting that cyclic mononucleotides, such as cAMP and cGMP, are not involved in curine effect. In confocal experiments, curine inhibited the rise on the [Ca2+]i induced by KCl (60 mM) in dispersed vascular smooth muscle cells. In reference to reticuline (3 300 μM) was verified that alkaloid agonized CaCl2 and KCl-induced contractions and elicited vasorelaxation in aortic rings. In whole-cell configuration, reticuline reduced the voltage-activated peak amplitude of ICa,L in a concentration-dependent manner, but did not change the characteristics of current density versus. voltage relationship. Reticuline shifted leftwards the steady-state inactivation curve of ICa,L, however this effect was not changed after application of dibutyryl cyclic adenosine monophosphate to the cell. In cells pretreated with forskolin, an adenylate cyclase activator, the addition of reticuline caused further inhibition of the Ca2+ currents suggesting an additive effect, indicating that cyclic mononucleotides were not involved. Taken together the results have shown that curine and reticuline elicits vasorelaxation due to the blockade of the L-type voltage-dependent Ca2+ current in rat aorta smooth muscle cells. The reported effect may contribute to the potential cardioprotective efficacy of curine and reticuline. Curina e reticulina são alcalóides isolados das cascas do caule e raízes de Chondrondendron platyphyllum e de Ocotea duckei Vattimo, respectivamente. Estudos anteriores demonstraram que esses alcalóides são capazes de induzir efeito vasodilatador em artéria mesentérica e aorta de rato, respectivamente, devido possível inibição dos canais para Ca2+ dependentes de voltagem (VGCC). O objetivo deste trabalho foi investigar o mecanismo vasodilatador de curina e reticulina realizando experimentações funcionais e moleculares. Foram utilizadas medidas de tensão em anéis de aorta de rato, e empregadas técnicas de patch-clamp e de microscopia confocal para estudos da ação desses alcalóides. Também foram utilizadas células A7r5, uma linhagem de células musculares lisas embrionária derivada de aorta torácica de rato, que foram usadas para medir as correntes de Ca2+ macroscópicas e a concentração de cálcio intracelular ([Ca2+]i), que foram avaliadas usando a técnicas de patch-clamp e microscopia confocal, respectivamente. Os principais resultados são: em anéis de aorta, curina (3 - 300 μM) antagonizou as contrações induzidas por KCl (60 mM) e Bay K8644 (3 x 10-7 M). Na configuração whole-cell patch clamp , curina reduziu a amplitude da corrente de cálcio do tipo L (ICa,L) de maneira dependente de concentração. Porém, curina não alterou as características das correntes na relação corrente-voltagem. A voltagem de ativação máxima para ICa,L não foi diferente em relação ao controle. Além disso, curina também não afetou a ativação no estado estacionário das ICa,L, mas deslocou a curva da inativação estacionária para potenciais mais negativos. No entanto, esse efeito promovido por curina não foi alterado na presença de IBMX, dbcAMP e 8- brcGMP, sugerindo que os mononucleotídeos cíclicos, como APMc e GMPc, não estão envolvidos no efeito da curina. Em experimentos com microscopia confocal curina inibiu os transientes de cálcio intracelulares, e reduziu o aumento de [Ca2+]i induzidos por KCl (60 mM) em células de músculo liso vascular. Em relação à reticulina (3 300 μM), foi verificado que esse alcalóide antagonizou as contrações induzidas por CaCl2 e KCl, provocando vasorelaxamento em anéis de aorta. Na configuração whole-cell patch clamp , reticulina também reduziu a amplitude das ICa,L de maneira dependente de concentração, mas não mudou as características da corrente na relação corrente-voltagem. A reticulina deslocou para potenciais mais negativos a curva de inativação estacionária para as ICa,L. Porém, esse efeito não foi alterado após a aplicação de dbcAMP e 8-brcGMP. Em células pré-tradadas com forskolina, um ativador da adenilil ciclase, a adição da reticulina causou uma inibição adicional das correntes de Ca2+ que sugere um efeito aditivo da reticulina, indicando que os mononucleotídeos cíclicos não estão envolvidos. Dessa forma, curina e reticulina provocaram vasorelaxamento, devido ao bloqueio das correntes de Ca2+ dependentes de voltagem do tipo-L em células de músculo liso, em cultura e recémdispersas, de aorta de rato, revelando que esses alcalóides têm um importante potencial como modelo químico para a concepção e posterior desenvolvimento de novos fármacos com propriedade protetora cardiovascular.

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Playl, Lauren A. "Sry Transcript Expression in Five Adult Male Rat Tissues and Correlation with Acsl3 Transcript Expression." University of Akron / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=akron1290632541.

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Vasconcelos, Flavio de. "Efeitos de a e b-neurotoxinas da peçonha do escorpião Tityus serrulatus sobre a liberação de catecolaminas, pressão arterial, captação de neurotransmissores e concentração de cálcio em células de músculo liso de aorta de ratos." Universidade de São Paulo, 2006. http://www.teses.usp.br/teses/disponiveis/60/60134/tde-21052007-095139/.

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Toxinas que atuam em canais para Na+ operados por voltagem são as principais responsáveis pelos efeitos tóxicos do envenenamento escorpiônico e podem ser divididas em duas classes: a- e b-neurotoxinas. TsTX-V e TsTX-I da peçonha de Tityus serrulatus (TsV) são, respectivamente, exemplos destas toxinas. Neste trabalho, foram avaliados os efeitos da TsV e destas toxinas sobre a pressão arterial média (PAM) e liberação de catecolaminas em ratos conscientes e não imobilizados, previamente cateterizados, bem como a captação de GABA, dopamina (DA) e glutamato (Glu) em sinaptosomas isolados de cérebro de ratos e a concentração citoplasmática de Ca+2 ([Ca+2 ]C) em células de músculo liso vascular de aorta de ratos. As toxinas foram isoladas por cromatografia de troca iônica (TsTX-I) seguida por CLAE de fase reversa (TsTX-V). As toxinas (15 e 30 g/kg) e TsV (50 e 100 g/kg) foram injetadas intravenosamente. A PAM foi monitorada continuamente através do cateter femoral. Os níveis plasmáticos de adrenalina (ADR) e noradrenalina (NA) foram determinados por CLAE de fase reversa com detector eletroquímico, em 10 min antes e 2,5, 30 e 90 min após os tratamentos. Efeitos pressores máximos foram observados em 2,5?3,5 min. TsV induziu um intenso aumento de longa duração na PAM, bem como a TsTX-I. A TsTX-V mostrou efeitos pressores menores. TsV mostrou os maiores efeitos sobre a liberação de catecolaminas, seguido pela TsTX-I e TsTX-V com um efeito máximo em 2,5 min, seguido por uma gradual redução, permanecendo, todavia, maior que os controles. Embora ambas as classes de toxinas atuem em canais para Na+, TsTX-I mostrou efeitos mais significantes e intensos sobre a liberação de catecolaminas e pressão arterial que a TsTX-V. Parece que a toxicidade da TsTX-V não está somente relacionada à sua capacidade de liberar catecolaminas, indicando que outros neutrotransmissores podem estar envolvidos em sua toxicidade. Nem a TsV ou suas toxinas foram capazes de afetar a captação de 3H-Glu. TsTXI inibiu somente a captação de 3H-DA (IC50 = 28,41 nM). Por outro lado, TsV (0,43ng/mL) inibiu a captação de 3H-GABA e 3H-DA (~50%). TsTX-V mostrou IC50 = 9,37 nM e 22,2 nM para a captação de 3H-GABA e 3HDA, respectivamente. Esses efeitos foram abolidos pelo pré-tratamento com TTX, indicando o envolvimento de canais para Na+ neste processo. Na ausência de Ca+2 e em baixas concentrações de toxinas, a redução não é tão singnificante como na presença de Ca+2. TsTX-V não reduziu a captação de 3H-GABA em células COS-7 expressando os transportadores de GABA, GAT-1 e GAT-3, sugerindo que esta toxina reduz indiretamente o transporte. A redução da captação de 3H-GABA pelos sinaptosomas pode ser devido a rápida e intensa despolarização celular, como revelado por microscopia confocal em células de glioma C6. Assim, TsTX-V causou redução da captação de 3H-GABA e 3H-DA de uma maneira independente de Ca+2, não afetando diretamente os transportadores de GABA, mas em consequencia da despolarização, envolvendo canais para Na+ operados por voltagem. TsV e suas toxinas foram capazes de aumentar a ([Ca2+ ]C , provavelmente por interargir com canais para Na+. Quando comparado aos efeitos despolarizantes do KCl 60 mM (100 %), TsV (100 e 500 g/mL) exibiu um aumento de 49,60 ± 2,58 % e 103,66 ± 5,17 %, respectivamente, enquanto que a TsTX-I e TsTX-V (50 e 100 g/mL de cada) exibiu 43,92 ± 3,06 % e 121,8 ± 8,9 %; 52,56 ± 8,33 % e 79,5 ± 6,1 % de aumento, respectivamente. TsTX-I (100 g/mL) mostrou-se mais potente nesta preparação, visto que uma dose de 100 g/mL causou efeito muito mais intenso do que a TsTX-V na mesma concentração. É possível que as diferenças observadas sobre os efeitos induzidos pela TsTX-I e TsTX-V sejam conseqüência de alterações estruturais entre canais para Na+ presentes em vários tipos de tecidos e inervações. Voltage-gated Na+ channel toxins are mainly responsible for the toxic effects of scorpion envenoming and can be classified into two classes: a- and b-neurotoxins. TsTX-V and TsTX-I from Tityus serrulatus venom (TsV) are, respectively, examples of these toxins. In this work, were evaluate the effects of TsV and its toxins on mean arterial pressure (MAP) and catecholamines release in conscious unrestrained rats previously catheterized, as well as GABA, dopamine (DA) and glutamate (Glu) uptake in isolated rat brain synaptosomes and cytosolic Ca2+ concentration ([Ca2+ ]C) in vascular smooth muscle cells from rat aorta. Toxins were isolated by ion exchange chromatography (TsTX-I) followed by RP-HPLC (TsTX-V). The toxins (15 and 30 g/kg) and TsV (50 and 100 g/kg) were injected intravenously. MAP was continuously monitored through femoral catheter. Epinephrine (E) and norepinephrine (NE) plasma levels were determined by RP-HPLC with electrochemical detection, at 10 min before and 2.5, 30 and 90 min after treatments. Maximal pressor effects were observed at 2.5 3.5 min. TsV induced intense long lasting increase in MAP, as did TsTX-I. TsTX-V showed the lowest pressor effects. TsV showed the highest effects on catecholamines release, followed by TsTX-I and TsTX-V with maximal effect at 2.5 min, followed by a gradual reduction, however remaining higher than controls. Although both toxins act on Na+ channels, TsTX-I displayed significant and more intense effects on catecholamines release and blood pressure than TsTX-V. It seems that the toxicity of TsTX-V is not related only with its ability to release catecholamines, indicating that other neurotransmitters, may be involved in its toxicity. Neither the TsV or its toxins was capable to affect the 3H-Glu uptake. TsTX-I inhibited only 3H-DA uptake (IC50 = 28.41 nM). On the other hand, TsV (0.43ng/mL) inhibited both 3H-GABA and 3H-DA uptake (~50%). TsTX-V showed IC50 = 9.37 nM and 22.2 nM for 3H-GABA and 3H-DA uptake, respectively. These effects were abolished by pre-treatment with TTX, indicating the involvement of Na+ channels in this process. In the absence of Ca2+ and at low concentrations of toxin, the reduction is not as significant as in the presence of Ca2+. TsTX-V did not reduce 3H-GABA uptake in COS-7 cells expressing GABA transporters GAT-1 and GAT-3, suggesting that this toxin indirectly reduces the transport. The reduced 3H-GABA uptake by synaptosomes could be due to fast and intense cell depolarization as revealed by confocal microscopy of C6 glioma cells. Thus, TsTX-V causes reduction on 3H-GABA and 3H-DA uptake in a Ca2+-independent manner, not affecting directly GABA transporters, but, in consequence of depolarization, involving voltage-gated Na+ channels. TsV and its toxins were able to increase the ([Ca2+ ]C , probably by interact with Na+ channels. When compared to KCl 60 mM depolarizing effect (100 %), TsV (100 and 500 ?g/mL), showed an increase of 49.60 ± 2.58 % and 103.66 ± 5.17 %, respectively, whereas TsTX-I and TsTX-V (50 and 100?g/mL of each) showed 43.92 ± 3.06 % and 121.8 ± 8.9 %; 52.56 ± 8.33 % and 79.5 ± 6.1 %, respectively. TsTX-I (100 ?g/mL) showed most potent effects in this type of preparation, since induced most intense effect that TsTX-V in the same concentration. Thus, it is possible that the differences observed on the effects induced by both toxins are consequence of structural changes among Na+ channels present in several types of tissues and innervations .

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Barros, Ana Rodrigues. "Tributyltin (TBT) effects at a vascular level." Master's thesis, Universidade de Aveiro, 2016. http://hdl.handle.net/10773/16393.

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Mestrado em Toxicologia e Ecotoxicologia Organotins are an important class man made organometallic compounds and tributyltin (TBT) is one of the most studied chemicals within this class. TBT is a potent endocrine disruptor being also considered as an obesogenic, immunotoxic and neurotoxic compound. Humans were exposed to this and other organotin compounds as a consequence of their widespread commercial applications including plastic stabilizers, catalytic agents and industrial biocides. Their utilization as catalytic agents in the production of silicones leads to the presence of these chemicals in silicone based products including those used in biomedical applications such as breast implants and cardiac valves which may constitute a potential source of exposure. According to the World Health Organization cardiovascular diseases are sharply increasing and constitute the prime cause of death globally. Taking this into account, regulatory agencies, recommend the study of organotin compounds toxicity. Considering the limited number of studies on the cardiovascular effects of organotins, the present thesis aims to elucidate the effects of TBT at the vascular level. The study of TBT effect on the contractility of rat artery (aorta) was performed by the organ bath technique and the L-type calcium channels in A7r5 (cell line derived from the smooth muscle of embryonic rat aorta) was measured by whole-cell configuration of the patch clamp technique. The obtained results demonstrated that TBT seems to relax the rat aorta without endothelium contracted by noradrenaline and potassium chloride but this effect is not significantly different from the respectively ethanol control. The electrophysiological experiments demonstrated that the inhibition of the calcium current by the L-type calcium channels in the A7r5 vascular smooth muscle cells was also not significantly different, which suggests that probably the mode of action of TBT is more complex and involves other pathways. Os compostos orgânicos de estanho são uma importante classe de compostos organometálicos produzidos pelo homem, e o tributilestanho (TBT) é um dos químicos mais estudados dentro desta classe. O TBT atua como um potente disruptor endócrino, sendo também considerado como um composto obesogénico, imunotóxico e neurotóxico. A exposição humana a este e outros compostos orgânicos de estanho deve-se à sua vasta utilização em aplicações comerciais como estabilizadores de plásticos, agentes catalíticos e biocidas industriais. A sua utilização como agentes catalíticos na produção de silicones faz com que estes compostos estejam presentes em vários produtos à base de silicone, incluindo os usados em aplicações biomédicas como implantes mamários e válvulas cardíacas, o que pode constituir uma fonte potencial de exposição para os humanos. De acordo com a Organização Mundial de Saúde, as doenças cardiovasculares estão a aumentar e são consideradas como a principal causa de morte a nível mundial. Tendo isto em conta, as agências reguladoras recomendam o estudo da toxicidade dos compostos orgânicos de estanho. Considerando o número limitado de estudos sobre os efeitos cardiovasculares dos compostos orgânicos de estanho, o presente trabalho pretende elucidar os efeitos do TBT ao nível vascular. Os efeitos do TBT na contractilidade de artérias de rato (aorta) foram estudados pela técnica do banho de órgãos e a medição dos canais de cálcio tipo L foi realizada em A7r5 (linha celular de músculo liso vascular derivada de aorta embrionária de rato) através da técnica do patch clamp na configuração whole cell. Os resultados obtidos demonstram que o TBT parece induzir relaxamento nas artérias sem endotélio contraídas previamente com noradrenalina e com cloreto de potássio, mas esse efeito não é significativamente diferente do controlo de solvente usado. Nas experiências de eletrofisiologia a inibição das correntes de cálcio através dos canais de cálcio tipo L nas células A7r5 também não mostrou ser significativamente diferente do controlo, o que parece demonstrar que o modo de ação pelo qual o TBT induz efeito nas células vasculares é mais complexo e envolve outras vias.

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Veras, Robson Cavalcante. "Participação da via do óxido nítrico na resposta relaxante induzida por E- cinamaldeído-oxima em artéria mesentérica superior isolada de rato." Universidade Federal da Paraíba, 2009. http://tede.biblioteca.ufpb.br:8080/handle/tede/6737.

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Made available in DSpace on 2015-05-14T12:59:37Z (GMT). No. of bitstreams: 1 parte1.pdf: 2125844 bytes, checksum: f5e0174d3679c5bce4f74af8ed1b3d4f (MD5) Previous issue date: 2009-08-30 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES Decreased availability of NO in the vasculature promotes the progression of cardiovascular diseases and oximes represents a NO-donor group capable of to restore this defictIn rat superior mesenteric arterial rings, as non-aromatic oximes: diacetylmonoxime and dimetylglycone-oxime, as aromatic oximes: benzofenone-oxime, 4-Cl-benzofenone and cinnamaldheyde-oxime isomeric mixture were markedly less potent than tans-E-cinnamaldheyde-oxime (E CAOx) whose relaxation was concentration-dependent in denuded-endothelum pre-contracted rings with PHE (pD2 = 5,11 ± 0,05), or U46619 (pD2 = 5,03 ± 0,06), an tromboxanic agonist TP, or with A23187 (pD2 = 4,70 ± 0,06), an Ca2+ ionophore, beyond KCl 60mM (pD2 = 4,50 ± 0,06). The relaxation was not modified by endothelium or L-NAME (100 μM, NOS inhibitor), proadifen (30 M; inibidor do citocromos P450), ou de N-acetyl-L-Cysteyn (1 mM e 3 mM; an NO- scavenger). However, was affected by cytochromos P4501A1 and NADPH-dependent reductases inhibitor, 7ethoxyresorufin (7 ER, 10 μM; pD2 = 4,82 ± 0,07), and NO scavenger, PTIO (300 M; pD2 = 4,68 ± 0,11). Demonstrating that E-CAOx induces independent-endothelium relaxation with a possible NO production, mediated by NADPH-dependent reductases. These results corroborate with E-CAOx action of to increase DAF-T fluorescence, in rat aorta smooth miocytes, abolished by 7-ER pre-incubation. Futhermore, the Emax decrease caused by (Rp)-8pCPT-cGMPS (10 M; PKG inhibitor), plus potency reduction by ODQ presence (0,1 M; pD2 = 4,65 ± 0,07 e 10 M; pD2 = 4,41 ± 0,04), a soluble guanylyl-cyclase inhibitor, reforce the pathway NO/cGC/cGMP/PKG participation. On the other hand, the presences of KCl 20mM and TEA (1 mM; pD2 = 4,62 ± 0,04), a BKCa blocker, were capable of the interfering in response, but not 4-AP (1 mM; Kv blocker) and Glibenclamide (10 M; a KATP blocker). In ODQ (10 M) combinations, only KCl 20mM, interpose on Emax, suggesting that K+ channels contribution, majorly BKCa, is sGC-activation dependent. Due relaxing pre-contracted rings: with S(-)BayK 8644 (pD2 = 4,95 ± 0,05), a direct activator of dihydropiridine-sensitive Cav, and rings pre-contracted with PHE in the presence of Niphedipine (1 M), E-CAOx can also to be acting by inhibits Ca2+ influx through dihydropiridine-sensitive Cav or to interfere in contract mechanisms ulterior to Ca2+ entry, as is the case of Na+/Ca2+ exchanger. This hypothesis is justified by reduction in response due the Ni+2 presence (Na+/Ca2+ inhibitor). In conclusion, the data shown that E-CAOx was the more potent oxime investigated with NO production thougth NADPH-dependent reductases action and subsequentely pathway CGs/GMPc/PKG activation associated to BKCa activation, Cav inhibition and exchalenger Na+/Ca2+activation. Uma diminuição da disponibilidade do NO na vasculatura promove a progressão de doenças vasculares e as oximas representam um grupo de doadores de NO capaz de reestabelecer tal deficiência. Em anéis de artéria mesentérica superior isolada de rato, tanto as oximas não aromáticas: diacetilmonoxima e dimetilglioxima, quanto as oximas aromáticas: benzofenona-oxima, 4 Cl benzofenona-oxima e a mistura isômera de cinamaldeído-oximas foram menos potentes que trans-cinamaldeído-oxima (E-CAOx) cujo relaxamento foi dependente de concentração em anéis pré-contraídos com: FEN (pD2 = 5,11 ± 0,05), um agonista adrenérgico, ou com U46619 (pD2 = 5,03 ± 0,06), um agonista tromboxânico TP, ou com A23187 (pD2 = 4,70 ± 0,06), um ionóforo de íons Ca2+, além de KCl 60mM (pD2 = 4,50 ± 0,06). O relaxamento não foi modificado pela presença do endotélio ou de L-NAME (100 M; inibidor das sintases de NO), proadifeno (30 M; inibidor do citocromos P450), ou de N-acetil-L-cisteína (1 mM e 3 mM; seqüestrador de NO-). Entretanto, foi afetado pela presença do inibidor de citocromos P4501A1 e de redutases dependentes de NADPH, 7-Etoxi-resurofino (7-ER, 10 M; pD2 = 4,82 ± 0,07), e do sequestrador de NO, PTIO (300 M; pD2 = 4,68 ± 0,11). Demonstrando que E-CAOx causa um relaxamento independente de endotélio com possível produção de NO , mediado por redutases dependentes de NADPH. Tais resultados corroboram com a ação de E-CAOx em aumentar a fluorescência emitida por DAF-T, em mióciotos de aorta de rato, abolida pela presença de 7-ER (10 M). Além disso, a diminuição do efeito máximo de E-CAOx causada pela presença de (Rp)-8pCPT-cGMPS (10 M; inibidor da PKG), somada à diminuição da potência causada pelo ODQ (0,1M; pD2 = 4,65 ± 0,07 e 10M; pD2 = 4,41 ± 0,04), um inibidor da ciclase de guanilil solúvel (CGs), reforçam a participação da via NO/CGs/GMPc/PKG. Por outro lado, as presenças de KCl 20mM (pD2 = 4,78 ± 0,04) e de TEA (1 mM; pD2 = 4,62 ± 0,04), um bloqueador de BKCa, foram capazes de interferir na resposta, mas 4-aminopiridina (1 mM; bloqueador de Kv) e Glibenclamida (10 M; bloqueador de KATP) não. Em combinações com ODQ (10M), apenas KCl 20 mM, interferiu no Emax, sugerindo que a contribuição dos canais para K+, principalmente dos BKCa, é dependente da ativação da CGs. Por relaxar anéis pré-contraídos com S(-)BayK 8644 (pD2 = 4,95 ± 0,05), um ativador direto dos Cav sensíveis à diidropiridinas, e anéis pré-contraídos com FEN na presença de nifedipino (1 M; inibidor dos Cav), E-CAOx pode também estar atuando por inibir o influxo de íons Ca2+ ou interferir em mecanismos contráteis posteriores à entrada de Ca2+, como é o caso do trocador Na+/Ca2+. Tal hipótese é justificada pela redução da resposta provocada pela presença do Ni+2 (inibidor do trocador Na+/Ca2+). Em conclusão, os dados demonstram que E-CAOx foi a oxima investigada mais potente e que produz NO via ação das redutases dependentes de NADPH com subseqüente ativação da via CGs/GMPc/PKG associada à ativação dos BKCa, inibição dos Cav e ativação do trocador Na+/Ca2+.

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BOULANGER, SAUNIER CHANTAL. "Phosphorylation d'une proteine de 16 kda par la proteine kinase dependant de l'amp cyclique et par la proteine kinase c dans la membrane plasmique des myocytes d'aorte de rat." Strasbourg 1, 1986. http://www.theses.fr/1986STR13158.

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Barandier, Christine. "Potentiel thérapeutique du manganèse et de l'un de ses dérivés synthétiques sur le système cardiovasculaire." Université Joseph Fourier (Grenoble), 1998. http://www.theses.fr/1998GRE10238.

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Le present travail qui s'inscrit dans le cadre general des etudes consacrees a la protection pharmacologique des tissus cardiaque et vasculaire au cours de la reperfusion post-ischemique, comprend deux parties principales. La premiere a ete realisee sur un modele d'ischemie/reperfusion myocardique sur un modele experimental de coeur isole de rat. Les resultats sont exprimes en termes de donnees fonctionnelles, metaboliques et ultrastructurales. La seconde partie est une etude pharmacologique menee sur un modele d'anneaux d'aorte isolee de rat et comporte essentiellement des mesures de contractilite vasculaire. Dans la premiere partie, nous avons etudie l'effet protecteur du chlorure de manganese sur la recuperation post-ischemique du myocarde. Nous avons demontre que le manganese, administre durant la phase precoce de la reperfusion, ameliore la recuperation metabolique et fonctionnelle, vraisemblablement par le biais d'une protection antioxydante de la membrane des cardiomyocytes. Nous avons egalement mis en evidence un effet protecteur du manganese administre avant la periode d'ischemie sur la fonction et l'ultrastructure du myocarde post-ischemique. Dans la seconde partie de notre travail, nous avons montre qu'euk8, un compose de type salen-manganese presentant de fortes activites sod et catalase, exerce in vitro un effet vasorelaxant dose-dependant, non medie par une simple protection antioxydante de no, mais essentiellement du a une activation de l'adenylate cyclase et de la guanylate cyclase soluble des cellules musculaires lisses vasculaires. Enfin, une etude des effets vasomoteurs du manganese nous a amenes a conclure qu'il induit une relaxation par le biais de mecanismes plus complexes qu'une simple protection antioxydante de no et qu'un simple effet antagoniste calcique direct sur les cellules musculaires lisses vasculaires.

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Khelili, Smaïl. "Synthèse et étude pharmacologique d'activateurs de canaux K+/ATP dérivés des 1,2,4-benzothiadiazine-1,1-dioxydes." Grenoble 1, 1993. http://www.theses.fr/1993GRE10210.

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Le but de cette these est de synthetiser et d'etudier les proprietes pharmacologiques d'activateurs potassiques sensibles a l'atp. Ces activateurs derivent de la 1,2,4-benzothiadiazine-1,1-dioxyde qui comporte un reste sulfonyluree sur differentes positions de cet heterocycle. Dans la premiere partie, nous abordons les proprietes pharmacologiques des canaux potassiques et leur classification, ainsi que celles des composes les plus importants modulant ces canaux. En particulier, nous decrivons les 1,2,4-benzothiadiazine-1,1-dioxydes et les sulfonylurees, dont nous rappelons egalement les methodes de syntheses. La deuxieme partie de la these comporte quatre chapitres: dans le premier nous faisons le point sur les differents schemas de syntheses adoptes pour aboutir aux molecules cibles; le deuxieme chapitre comporte une etude spectrale de quelques composes finaux notamment par rmn du proton et par rmn du carbone 13; le troisieme chapitre comprend l'etude pharmacologique de quelques composes testes sur des anneaux d'aorte de rats; enfin, la partie experimentale decrit les modes operatoires mis en uvre pour preparer les composes intermediaires et cibles ainsi que les methodes de purification et d'identification que nous avons utilisees

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Dantas, Bruna Priscilla Vasconcelos. "Participação dos canaisTRP nos efeitos cardiovasculares induzidos por carvacrol em ratos." Universidade Federal da Paraíba, 2010. http://tede.biblioteca.ufpb.br:8080/handle/tede/6854.

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Made available in DSpace on 2015-05-14T13:00:13Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 2275378 bytes, checksum: fcb4196c739d83997818dc074daf738f (MD5) Previous issue date: 2010-03-11 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES The pharmacological effects of carvacrol, a monoterpenoid phenol, on the cardiovascular system were studied in normotensive rats, using in vivo and in vitro techniques. In superior mesenteric artery rings isolated from rats with functional endothelium carvacrol (10-8 - 3 ₓ 10-4 M) concentration-dependently relaxed phenylephrine-induced contractions (pD2 = 4.59  0.02, MR = 103.03  1.5%, N=8) and this effect was not altered after removal of the endothelium (pD2 = 4.36  0.02, MR = 111.03  4.8%, N=8), suggesting that the vasorelaxant response induced by carvacrol appears to be independent of vascular endothelium. Furthermore, carvacrol antagonized the vasoconstriction induced by high K+ solution (Tyrode with 80 mM of KCl) (pD2 = 4.12  0.01, MR = 94.38  3.97%, N=6), inhibited contraction elicited by CaCl2 in depolarizing (KCL 60 mM) nominally without Ca2+ medium out carvacrol also antagonized the contractions induced by the L-type Ca2+ channel agonist, S(-)-Bay K 8644 (pD2 = 4.537  0.023, MR = 9.8  3.58%, N=6), indicating that the vasodilatation involve probably the inhibition of Ca2+ influx through L-type voltage-dependent calcium channels (Cav type-L). Additionally, carvacrol antagonized the contractions induced by CaCl2 in nominally without Ca2+ medium in the presence of PHE and nifedipine, suggesting a possible inhibition of calcium influx by store operated channels (SOC), receptor operated channels (ROC) and/or TRP channels. Interestingly, in a depolarizing (KCL 60 mM) nominally without Ca2+ medium and in the presence of nifedipine, carvacrol also inhibited the contraction induced by CaCl2, suggesting a probable inhibition of SOC and/or TRP channels. To evaluate the involvement of TRP channels in the vasorelaxant effect induced by carvacrol, non-selective inhibitors were used. No change in the relaxation response was observed in the presence of ruthenium red (pD2= 4.31  0.029, N=6), however, the effect induced by carvacrol was potentiated by La3+ (pD2 = 5.231  0,04, N=6), Gd3+ (pD2 = 4.97  0.02, N=6) or Ni2+ (pD2 = 5.079  0.02, N=6), furthermore, Mg2+ (pD2 = 4.168  0.021; MR = 81.12  4.03%, N=6) attenuated the relaxation elicited by carvacrol, suggesting that monoterpenoid may to action on TRPC1, TRPC3, TRPC6 and TRPM7 channels. Carvacrol also induced hypotension and bradycardia in non-anesthetized normotensive rats. In conclusion, these results suggest that carvacrol induced vasorelaxant effect in superior mesenteric artery rats isolated probably inhibiting Ca2+ influx by Cav, SOC (TRPC1), ROC (TRPC1 or TRPC6) and TRPM7 channels. Moreover, the effects induced by carvacrol in normotensive non-anesthetized rats showed a hypotensive and bradycardic activity. Os efeitos farmacológicos de carvacrol, um fenol monoterpenóide, sobre o sistema cardiovascular, foi estudado em ratos normotensos, usando técnicas in vivo e in vitro. Carvacrol (10-8 - 3 ₓ 10-4 M) induziu vasorelaxamento dos anéis de artéria mesentérica superior isolada de rato pré-contraídos com 10 μM FEN (pD2 = 4,59  0,02, Emáx = 103,03  1,5%) na presença do endotélio funcional e esse efeito não foi alterado após a remoção do endotélio (pD2 = 4,36  0,02, Emáx = 111,03  4,8%), sugerindo, portanto, que a resposta vasorelaxante induzida por carvacrol parece ser independente do endotélio vascular. Interessantemente em anéis pré-contraídos com KCl 80 mM (pD2 = 4,12  0,01, Emáx = 94,38  3,97%), observou-se uma diminuição na sua potência e na sua eficácia farmacológica, sugerindo um passo comum na via que seria um aumento citosólico dos níveis de cálcio. Adicionalmente, carvacrol antagonizou, de maneira dependente de concentração, as contrações induzidas por CaCl2 em meio despolarizante nominalmente sem Ca2+ e induziu relaxamento das contrações induzidas pelo S(-)-Bay K 8644 (pD2 = 4,537  0,023, Emáx = 91,8  3,58%) com uma diminuição na sua eficácia farmacológica, sugerindo uma inibição do influxo de cálcio por canais de Ca2+ tipo-L. Além disso, antagonizou as contrações induzidas por CaCl2 em meio nominalmente sem cálcio, na presença de FEN e nifedipina, sugerindo uma provável inibição do influxo de cálcio por SOC, ROC e/ou canais TRP. Como também, em um meio despolarizante e nominalmente sem cálcio na presença de nifedipina esse mesmo antagonismo foi observado, ressaltando a provável inibição dos SOC e/ou canais TRP. Para avaliar a participação dos canais TRP, as preparações foram incubadas com La3+ (pD2 = 5,231  0,04) , Gd3+ (pD2 = 4,97  0,02) e Ni2+ (pD2 = 5,079  0,02) onde seu efeito foi potencializado sugerindo sua ação sobre os canais TRPC e ao utilizar magnésio (pD2 = 4,168  0,021 e Emáx = 81,12  4,03%) tanto sua potência quanto sua eficácia farmacológica foi atenuada, sugerindo inibição do canal TRPM7. Nos estudos in vivo, em ratos normotensos não anestesiados, carvacrol produziu hipotensão e bradicardia. Em conclusão, esses resultados sugerem que carvacrol induz efeito vasorelaxante em anéis de artéria mesentérica superior isolada de rato por inibir provavelmente TRPM7, como também inibir o influxo de cálcio por Cav, SOC, ROC e ou TRPC1 e 6. Além disso, os efeitos induzidos por carvacrol em ratos normotensos não anestesiados mostrou uma atividade hipotensora e bradicárdica.

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38

Cheng, Yu-Wen, and 鄭幼文. "Polycyclic aromatic hydrocarbons-induced vasorelaxation in rat aorta." Thesis, 1999. http://ndltd.ncl.edu.tw/handle/52390419926054837039.

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博士 國立臺灣大學 毒理學研究所 87 The use of transporting vehicles has facilitated the improvement of human life since industrial revolution. However, the pollutant from the exhaust of vehicles have created a serious health problem especially in urban cities, including the cardiovascular diseases. For example, carbon monooxide, carbon dioxide and some polycyclic-aromatic hydrocarbons (PAHs), such as benzo(a)pyrene, dimethylbenzo(a)anthracene, and 3-methylchlorolanthracene, have been shown to induce artherosclerosis in animals. However, the studies concerning the effect of low-molecular weight polycyclic aromatic hydrocarbons on cardiovascular system remain scarce. In this study, we tested the effect of PAHs on the vascular-reactivity using the thoracic aorta isolated from rat. The PAHs used in this study include naphthalene, acenaphthalene, acenaphthylene, fluorene, fluoranthene, anthracene, chryscene, pyrene and benzo(a)pyrene. We found that the lower molecular weight polycyclic aromatic hydrocarbons, such as naphthalene, acenaphthylene, fluorene and fluoranthene caused vasorelaxation on phenylephrine pre-contracted rat aorta but not benzo(a)pyrene. These four polycyclic aromatic hydrocarbons can also inhibit phenylephrine-induced vasocontraction in an endothelium-dependent manner at lower concentrations, 1~50 uM. Th effect of these PAHs can be inhibited by prior treatment with the nitric oxide synthase inhibitor, L-NAME, and guanylate cyclase inhibitor, methylene. These data suggested that the effect exerted by these PAHs might be nitric oxide related. These four PAHs can elevate the cGMP content in smooth muscle cells of rat aorta in a calcium dependent manner. We conclude that these four PAHs will induce extracellular calcium influx, activate calcium-dependent endothelial nitric oxide synthase, result in NO production. The NO generated from endothelium cell will then activate guanylate cyclase and increase cGMP formation in smooth muscle cells, which causes vasorelaxation. In addition, higher concentration of PAHs (50 uM ~ 300 uM) can induce vasorelaxation in the denuded aorta. We found naphthalene and acenaphthylene concentration-dependently inhibited phenylephrine-induced vasocontraction and inositol-trisphosphate formation in denuded rat aorta. However, fluorene and fluoranthene did not affect phenylephrine-induced inositol-trisphosphate formation. Many PAHs exert their toxic effect through the bioactivation by P450 related metabolic pathway. By using several kwown P450 inhibitors, we found that the effects of these four PAHs on rat aorta might not be P450 related. We also investigated the effect of motorcycle exhaust particlate extract (MEPE) on thoracic aorta isolated from rat. We found that, MEPE concentration-dependently inhibited the phenylephrine induced vasocontraction in an endothelium-independent manner, possibly by inhibiting the insitol-trisphosphate formation. In addition to the inhibition effect on phenylephrine-response, MEPE also concentration-dependently impaired the acetylcholine-induced vasorelaxation. This inhibitory effect induced by MEPE can be reversed by pretreatment of superoxide dismutase. These data indicate that this inhibitory effect might be caused by the superoxide anion produced from MEPE which will then impaire the nitric oxide-induced vasorelaxation. Effects of these four PAHs and MEPE on blood pressure were also studied in Wistar rats. Data suggested that these four PAHs and MEPE not only induced vasorelaxation in vitro, they also supressed blood pressure in a dose-dependent manner in vivo. In conclusion, for the first time, we have found that low-molecular weight PAHs, including naphthalene, acenaphthylene, fluorene, fluoranthene, will affect the vascular-reactivity in vitro. Furthermore, we have also demonstrated that some components in the MEPE will affect the physiological function of isolated rat aorta. Our data have also shown that these compounds will supress blood pressure in vivo. The chronic effect and the possible links to the cardiovascular disease of these PAHs and MEPE still need further investigation.

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Tseng, Hsiang-Wen, and 曾湘文. "The Vasorelaxing Mechanisms of Rutamarin Alcohol in Rat Thoracic Aorta." Thesis, 2001. http://ndltd.ncl.edu.tw/handle/94664114157860004755.

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碩士 國立陽明大學 藥理學研究所 89 Abstract We have examined both the hypotensive effect and the mechanisms of vasorelaxation of rutamarin alcohol (RA), a dihydrofuranocoumarins compound isolated from Ruta graveolens L. of Rutaceae. Intravenous bolus injections of RA (0.25-1.25 mg/kg) in anesthetized Sprage-Dawley rats produced dose-dependent hypotensive effects. In isolated rat thoracic aorta rings with or without endothelium, RA (10-7 ~ 10-4 M) relaxed phenylephrine (PE, 10-6M)- or KCl (60 mM)-induced vasocontractions. The vasorelaxing effect was greater for intact than for endothelium-denuded tissues. Pretreatment with RA (10-6 ~ 5X10-5 M) for 15 min shifted the concentration-response curves for PE (10-9 ~ 10-5M) to the right and reduced the maximal responses. Ca2+-free Krebs’ solution RA (3X10-5 ~5X10-5M) suppressed the sustained contraction stimulated by phorbol 12-myristate 13-acetate (PMA, protein kinase C activator, 10-6 M). RA (3X10-5, 5X10-5 M) also attenuated the norepinephrine (NE, 10-6M)-induced contraction in Ca2+-free solution. In Ca2+-depleted, NE-, PMA- or high K+-treated aortic rings, preincubation with RA attenuated the Ca2+-induced contraction in a concentration-dependent fashion. In RA caused a rightward shift of the vasorelaxant response curve in endothelium-intact rings by N-nitro-L-arginine (nitric oxide synthase inhibitor, 10-4M, 15 min), methylene blue (guanylyl cyclase inhibitor, 5X10-5M, 5 min), and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, specific soluble guanylyl cyclase inhibitor, 10-6M, 15 min) pretreatment. Tetraethylammonium chloride (Ca2+-activated potassium channel blocker, 10-6M, 60 min) pretreatment did not reverse the vasorelaxation of RA. Additionally, RA (10-4M, 30 min) significantly increased nitric oxide (NO) release in cultured endothelial cells. Receptor binding assay indicated that RA competed with the dihydropyridine (DHP) ligand with a Ki value of 111±54 microM. However, RA did not interact with rat heart a1-adrenoceptors. In cultured vascular smooth muscle cells, the cell viability was not affected treatment with RA (10-6 ~10-4M) for 1 hr or 5X10-5 M for 1 to 24 hr. Taker together, the present results suggested that the vasorelaxing effect of RA was mediated mainly through inhibiting PKC, Ca2+ release and Ca2+ influx, through receptor-operated Ca2+ channels and voltage-dependent Ca2+ channels in vascular smooth muscle. Although the contribution seemed to be minor in nature, increase in NO release in endothelial cells, was also involved. The regulation of vascular smooth muscle cells and endothelial cells acts simultaneously to cause vasorelaxarion which could account, at least a part, for the hypotensive action.

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Novýsedláková, Alena. "The in vitro effects of selected isoflavonoids on isolated rat aorta." Master's thesis, 2017. http://www.nusl.cz/ntk/nusl-370988.

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Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Alena Novýsedláková Supervisor: PharmDr. Jana Pourová, PhD. Title of Thesis: In vitro effects od selected isoflavonoids on isolated rat aorta Abstract: The aim of this study was to determine whether the selected isoflavonoids are able to vasodilate aorta, what structural features might be responsible for a relaxing activity and estimate the mechanism of action. The experiment we carried out the classical in vitro method on the isolated rat aorta, and the results evaluated by the computer program GraphPad. Only glycitin did not show statistically significant relaxation of blood vessels, which can be attributed to ineffective glycosidic form. Other izoflavonoids- glycitein, daidzein and tectorigenin seem to be promising in terms of potential vasodilatation. Further studies would be needed to verify also the in vivo effects. Likely structural features include the hydroxy group at 7-position and a methoxy group at position 8 of the core od isoflavonoids. The mechanism of action is not yet known, but most likely appears endothelium-dependent mechanisms, alpha 1 receptor antagonism and agonism of muscarinic M3 receptor. It may be also involved in the effect of the antioxidant and...

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Lin, Chung-Yin, and 林聰穎. "Synthesis and Vasorelaxant Activity of Naphthopyrans on Isolated Rat Thoracic Aorta." Thesis, 2000. http://ndltd.ncl.edu.tw/handle/13148980448419198809.

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碩士 中國文化大學 應用化學研究所 88 Potassium channel openers, such as cromakalim, are potent smooth muscle relaxants which have been shown to have potential therapeutic application in a variety of cardiovascular and bronchopulmonary diseases, particularly in asthma, hypertension, and urinary incotinence. Cromakalim, the first benzopyran type potassium channel opener, was found as a potent antihypertensive agent in 1986. After that there have been numerous reports on modification of substituents at different positions of benzopyran ring, but few reports on modification of the benzopyran nucleus itself. In the course of our studies on new hypotensive potassium channel openers, we considered replacing the benzopyran ring with naphthopyran ring and this change would not affect the electronic nature of the aromatic ring. Therefore, a new series of 4-substituted naphthopyrans (24-27, 33-35, 39-41) have been prepared and their vasorelaxant activities have been evaluated. Among them, 25a showed more potent vasorelaxant activity (EC50= 0.22 μM) on isolated rat thoracic aorta precontracted with phenylephrine.

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Ku, Tse-Cheng, and 顧澤承. "Vascular effects of Apocynum venetum leaf extract in rat thoracic aorta." Thesis, 2011. http://ndltd.ncl.edu.tw/handle/92440536478474846608.

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碩士 中國醫藥大學 基礎醫學研究所碩士班 99 Abstract Apocynum venetum, also known as luobuma, has been used as the sole ingredient in antihypertensive tea in China. In our preliminary study, we found Apocynum venetum leaf extract (AVLE) could elicit vasorelaxation but at high dosage of AVLE could reverse the AVLE- evoked vasorelaxation. In this study, we investigate the vascular tension effect of this herb extract in isolated rat thoracic aorta. AVLE 10 µg/ml and carbachol (CCh) could elicit endothelium- dependent vasorelaxation. AVLE has shown the long-lasting vasodilatation which that effect could inhibit the phenylephrine (α1-adrenergic receptor agonist; PE)-evoked vasoconstriction but could not inhibit potassium cholride-evoked vasoconstriction. The AVLE-evoked long-lasting vasodilatation could be reversed by L-NAME (nitric oxide synthase inhibitor). The concentration above AVLE 30 µg/ml (high dosage) could reverse AVLE evoked long-lasting vasorelaxation. Combined SOD and catalase could inhibit the reverse AVLE evoked vasorelaxation, but less inhibits effect by catalase only. In summary, our results indicate the mechanism of relaxative effect on vascular muscle might be related to endothelium-dependent NO mediated and the high dosage of AVLE evoked vasoconstriction might be mediated by superoxide anions in isolated rat aorta. Key words: luobuma, AVLE, antihypertensive tea, aorta, EDRF, vasoconstriction, L-NAME, SOD, catalase, NO, superoxide anions.

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43

趙俊迪. "Studies of The Vasodilating Effect of Berberine in Rat Denuded Aorta." Thesis, 1994. http://ndltd.ncl.edu.tw/handle/28437504607721097696.

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碩士 高雄醫學大學 醫學研究所 82 Berberine, an alkaloid isolated from the Chinese herb Huanglian (the rhizome of Coptis Chinensis Franch) has been reported to have a vasodilating effect in rats and dogs. The vasodilating effect of berberine was assessed by adding phenylephrine (PE) or high potassium in the presence of various concentration of berberine. The effect of berberine on PE-sensitive Ca store was evaluated by adding PE to aorta in Ca-free solution. A7r5 smooth muscle cells with whole-cell patch clamp technique were used to study the effect of berberine on Ica, L of smooth muscle cells. The results show that berberine (0.5-50 uM) inhibited aorta contraction induced by PE, but did not decrease the high potassium induced contraction. Berberine (30 uM) did not change the Ica, L of A7r5 cultured smooth muscle cells. Conclusion : 1. The vasodilating effect of berberine is independent of the lining endothelium. 2. Berberine does not have significant inhibition on voltage dependent L-type calcium channel in A7r5 smooth muscle cells. And Nifedipine significantly inhibits L-type calcium channel. 3. The vasodilating effect of berberine appears to be related to the inhibition of phenylephrine-induced calcium release from sarcoplasmic reticulum. 4. To observe the effect of berberine on the potassium current of smooth muscle cells is helpful to understand the mechanism of vasodilating effect of berberine.

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Huang, Tung-Yi, and 黃東益. "The Endothelial [Ca2+]i Signaling and Vascular Responsiveness in Rat Aorta In Situ." Thesis, 2002. http://ndltd.ncl.edu.tw/handle/u9nv5a.

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博士 國立成功大學 基礎醫學研究所 90 Endothelial cells are heterogeneous in their surface receptors, signaling pathways, intrinsic genetic programs and physiological functions. Microvascular endothelium cultured from the brain, liver and other organs each expresses distinct patterns of cell surface markers, protein transporters, and intracellular enzymes. Many human vascular diseases are restricted to specific types of vessels. More and more evidence have shown that the preferential occurrences of vascular diseases might result from certain molecules expressed at particular endothelium. Although study on the endothelial heterogeneity might provide valuable information on the target specificity and reveal the possible mechanism of the diseases and the selectivity for future vascular therapeutics, the information regarding local endothelial heterogeneity is largely lacking at the present time. 　Since fluid shear stress and vessel thickness change drastically at the intercostal orifice of aorta, endothelial cells surrounding the orifice are exposed to environmental conditions that are locally heterogeneous. The endothelial phenotype of that particular area may be subjected to some modification resulting from intrinsic genetic programs or the adaptation to the environment. It is plausible that the receptor portraits and signaling pathways are modified to some extent in that region. The endothelial cytosolic free Ca2+ concentration (EC [Ca2+]i) signaling is the most common signaling pathway mediating endothelial functions. The phenotypic characteristics might change drastically if EC [Ca2+]i signaling undergoes significant modulations in response to environment challenges. The primary goal of this study was to examine the regional heterogeneous response of endothelial [Ca2+]i signaling in intact rat aortic endothelium. 　　By studying the endothelial [Ca2+]i signaling in intact rat aorta, the author revealed that there is agonist specific heterogeneous [Ca2+]i signaling in intact rat aortic endothelium. Acetylcholine or histamine reversibly activated the vascular endothelium by eliciting M3 or H1 receptor-mediated [Ca2+]i elevation, respectively. The acetylcholine-evoked endothelial [Ca2+]i elevation at the branch site (intercostal orifice) was much more pronounced than that at the non-branch area. However, endothelium at the branch site was relatively insensitive to histamine. Both acetylcholine-sensitive and histamine-sensitive endothelial cells were arranged in belts aligned along flow lines and were intercalated with each other. Endothelial cells located at the non-branch site showed drastically heterogeneous [Ca2+]i responses to a fixed concentration of either acetylcholine or histamine, differing by two orders of magnitude in individual cells. 　The control of vascular tone by endothelial cells is one of the most important functions of vascular endothelium. Although endothelial derived relaxing factors could be released in a calcium independent manner under some circumstances, the central dogma of endothelial-modulated vasodilatation remains the calcium dependent. In response to various chemical and physical stimuli, an elevation of [Ca2+]i level followed by the activation of calcium-dependent enzymes/channels was observed in most cases. Nevertheless, the quantitative relationship between EC [Ca2+]i and vascular tone remains unclear at present time. Therefore, another specific aim of this thesis was to study the role of EC [Ca2+]i signaling in modulation of vascular tone in rat aortae. 　The role of endothelial [Ca2+]i in regulating vascular tone was examined by using a novel method that allows simultaneous recording of endothelial fura-2 ratio images and vascular displacement in rat aortic segments in a flow system. Since neither endothelial [Ca2+]i elevation nor vasodilatation was observed during or at the onset of flow, the calcium dependent/independent of flow effects was insignificant under our experimental conditions. In an en face preparation pre-contracted with phenylephrine, endothelial [Ca2+]i elevation followed by vasorelaxation was observed upon application of either acetylcholine or ionomycin. Vascular tone was highly sensitive to endothelial [Ca2+]i changes, especially near the basal level; while low doses of agonists induced minor increases of endothelial [Ca2+]i (<200 nM) and concomitant vasorelaxation close to maximal value, high doses of agonists elevated endothelial [Ca2+]i to mM range with small additional vessel dilatation. When endothelial [Ca2+]i was plotted against the vasorelaxation, the curves were almost identical for both acetylcholine and ionomycin treatments. Calcium-free solution reduced basal endothelial [Ca2+]i and induced a concomitant vascular contraction. Although inhibitors for endothelium-dependent relaxing factors did not prevent endothelial [Ca2+]i changes, they abolished both agonist-induced vasodilatation and calcium free solution-induced vessel contraction. While 40 mM BAPTA abolished both agonist-induced endothelial [Ca2+]i elevation and vasodilatation, 20 mM BAPTA prevented the acetylcholine-induced endothelial [Ca2+]i elevation to more than 150 nM without altering the maximal vasodilatation. These results indicate that endothelial [Ca2+]i level seems to serve as an integrating signal in both basal and stimulated states. 　In conclusion, endothelial [Ca2+]i signaling is heterogeneous in the branch area regarding its agonist-specificity, signaling amplitude, and pattern. As EC [Ca2+]i level was an integrating signaling in vasodilatation, the author proposed that there might be an agonist specific regulation of blood distribution especially during stress situation such as exercise.

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45

Hsiao, Shih-Hao, and 蕭士豪. "Effects of Acrylamide on Isolated Rat Aorta and Mouse Phrenic-nerve Diaphragm Toxicity." Thesis, 2019. http://ndltd.ncl.edu.tw/cgi-bin/gs32/gsweb.cgi/login?o=dnclcdr&s=id=%22107NCHU5252009%22.&searchmode=basic.

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碩士 國立中興大學 食品安全研究所 107 Purpose: Acrylamide (AA) can be formed during high-temperature frying or baking in the presence of both free asparagine and reducing sugars. It is known that AA displays genotoxicity, carcinogenicity, neurotoxicity and reproductive toxicity in laboratory animals. However, the related mechanisms of acrylamide-induced vasotoxicity and neuro-muscular toxicity are still unclear. This aim of this study was to investigate the possible mechanisms of vasotoxicity and neuro-muscular toxicity of acrylamide. Method: Vascular toxicity was studied by using an isolated rat aortic ring model. The aortic rings were divided into different groups, which included: a group of those with or without endothelium, a nitric oxide synthase (NOS) inhibition group (L-NAME), an acetylcholine receptor (AChR) inhibition group (atropine and mecamylamine) and an extracellular calcium inhibition group. Changes of muscle tension were used as an indicator of vasotoxicity. Neuromuscular toxicity was assessed using the phrenic nerve-diaphragm model, and experiments were performed using the AChR inhibition group and extracellular calcium inhibition group. Muscle stimulation changes were used as an indicator of neuro-muscular toxicity and muscle contracture. Results: The results revealed that acrylamide significantly caused relaxation in a dose-dependent manner when incubated with phenylephrine (PE) pre-induced endothelium-intact and -denuded aortic rings. Meanwhile, the half effective concentration (EC50) values of acrylamide in endothelium-intact and -denuded aortic rings were 57.5 mM and 85.3 mM, respectively. Acrylamide-induced relaxation could be significantly attenuated by adding NOS inhibitors and AChR inhibitors (mecamylamine). On the contrary, the other groups displayed no significant inhibition. The phrenic nerve-diaphragm results revealed that acrylamide caused reduced stimulation and muscle contracture. There was no significant difference in the AChR inhibition group, and removal of extracellular calcium did not inhibit muscle contracture. These results indicate that vasodilatation induced by acrylamide is regulated by nitric oxide synthase via aortic endothelium. The regulation of muscle stimulation and contracture is caused by nicotinic acetylcholine receptors.

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Beránková, Anna. "Účinky vybraných látek in vitro na izolované aortě potkana." Master's thesis, 2018. http://www.nusl.cz/ntk/nusl-380482.

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Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Anna Beránková Supervisor: PharmDr. Jana Pourová, Ph.D. Title of diploma thesis: The in vitro effects of selected substances on isolated rat aorta Flavonoids are a numerous group of secondary plant metabolites. Flavonoid compounds are substances widely extended in nature and many of them have a positive influence on human health, primarily for their vasodilatory, antioxidant and anti- inflammatory effects. Three substances were selected for this diploma theses: two substances of isoflavonoid group, genistin and genistein, and the end product of genistein metabolism, 4-ethylphenol. The aim of this work is examination of vasorelaxant effects of this substances in vitro. Vasorelaxing potential of tested substances was tested in vitro in isolated aortic rings of Wistar rat. The effect of increasing doses of individual substances in precontracted aortic rings with intact endothelium was measured. From the obtained values of vessel tension, the DRC curves and EC50 values were created. The results were evaluated. The results analysis shows, that genistein (EC50 2,903.10-5 M) had the most significant activity. Also genistin (EC50 4,045.10-4 M) and high doses of 4-ethylphenol (EC50 1,509.10-3 M) caused...

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Chin, Trow-Wey, and 秦作威. "Transendothelial Transport of Low Density Lipoprotein (LDL) in Association with Cell Death in Rat Aorta." Thesis, 1998. http://ndltd.ncl.edu.tw/handle/51704901055395896259.

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Hsun-HaoYeh та 葉訓豪. "Interleukin-1β-Induced Cellular Senescence of Vascular Smooth Muscle Cells Derived from Rat Abdominal Aorta". Thesis, 2019. http://ndltd.ncl.edu.tw/handle/r9baw3.

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Sloukgi, Tatiana. "Účinky vybraných flavonolygnanů silymarinu ex vivo na izolované aortě potkana." Master's thesis, 2020. http://www.nusl.cz/ntk/nusl-412345.

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Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Tatiana Sloukgi Supervisor: PharmDr. Jana Pourová, Ph.D. Title of Diploma Thesis: The effect of Silymarin Flavonolignans and their sulfated conjugates on blood vessels ex vivo. Silymarin flavonolignans have recently shown some positive effects on the cardiovascular system. In this work, we studied the vasodilatory effect on rat aorta ex vivo of three silymarin conjugates, silybin A-20-sulfate, silybin B-20-sulfate and 2,3- dehydrosilychristin-19-O-sulfate, and one parent flavonolignan 2,3- dehydrosilychristin. For each substance, a concentration response curve was created and the concentration that produces 50% of maximum relaxation was determined (EC50). All substances exerted very low or no vasodilatory activity. Finally, we focused on the mechanism of action of silybin A. We tested whether its vasorelaxant activity depends on the presence of intact endothelium. The vasorelaxant effect of silybin A on isolated rat aorta ex vivo was clearly endothelium-dependent.

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Yen-Cheng, Shih, and 施彥丞. "The role of AMP-activated kinase in the alpha-lipoic acid-induced vasodilation in rat aorta." Thesis, 2010. http://ndltd.ncl.edu.tw/handle/13267739156004999613.

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碩士 國防醫學院 藥理學研究所 98 AMP-activated protein kinase (AMPK) is a key regulator of cellular and whole-body energy homeostasis. Recently, some research reported that it could regulate the vasomotion of vascular smooth muscle. Alpha-lipoic acid, a medicine used to treat diabetic neuropathy, has been found it could affect activity of AMPK in hypothalamus, skeletal muscle, and adipose tissue. However, there is no study to investigate whether AMPK involves the vasomotion induced by alpha-lipoic acid in vascular smooth muscle. Thus, the aim of our study was to investigate the effect and possible mechanism of α-lipoic acid on AMPK protein expression and activity in A10 vascular smooth muscle cells and in rat thoracic aorta. According to the results, a series concentration of α-lipoic acid (10, 30, 50 µM) significantly increases AMPK activity in A10 vascular smooth muscle cells (A10 VSMC). This effects was possibly mediated by activation of calmodulin-dependent protein kinase kinase (CaMKK). In addition, a series concentration of α-lipoic acid (10, 30, 100 µM) significantly dilated the thoracic aorta rings in 8- and 16-week-old SHRs and 16-week-old WKYs. The vasodilaton in 16-week-old rats was greater than that in 8-week-old rats. Furthermore, pretreatment of N-nitro-L-arginine methyl ester (L-NAME) in aorta did not inhibit the relaxation induced by α-lipoic acid (100 µM) in 16-week-old WKYs and SHRs. On the other hand, pretreatment of compound C (AMPK inhibitor) in aorta significantly inhibited the relaxation induced by α-lipoic acid (100 µM) in 16-week-old SHRs. Besides, α-lipoic acid (100 µM) indeed activated AMPK in rat aorta smooth muscle. The phosphorylation of AMPKα in rat aorta smooth muscle was possibly mediated by activation of LKB1. In conclusion, α-lipoic acid significantly dilated aorta rings in a endothelium-independent manner and increased the AMPK activity in A10 vascular smooth cells and rat aorta smooth muscle. However, it seems that the mechanism between α-lipoic acid-induced AMPK activation in A10 VSMC and rat aorta smooth muscle were different: the former was mediated by the activation of CaMKK and the latter was mediated by activation of LKB1. However, the difference of signal transduction between A10 VSMC and rat aorta smooth muscle may associate with the different oxidative stress.

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