To see the other types of publications on this topic, follow the link: Endothelium and hyperpolarizing factors.
Journal articles on the topic 'Endothelium and hyperpolarizing factors'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'Endothelium and hyperpolarizing factors.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Sandow, Shaun L. "Factors, fiction and endothelium-derived hyperpolarizing factor." Clinical and Experimental Pharmacology and Physiology 31, no. 9 (2004): 563–70. http://dx.doi.org/10.1111/j.1440-1681.2004.04048.x.
Full text
2
Janssen, Luke J. "Are endothelium-derived hyperpolarizing and contracting factors isoprostanes?" Trends in Pharmacological Sciences 23, no. 2 (2002): 59–62. http://dx.doi.org/10.1016/s0165-6147(02)01890-4.
Full text
3
Campbell, William B., and John R. Falck. "Arachidonic Acid Metabolites as Endothelium-Derived Hyperpolarizing Factors." Hypertension 49, no. 3 (2007): 590–96. http://dx.doi.org/10.1161/01.hyp.0000255173.50317.fc.
Full text
4
Campbell, William B., and Kathryn M. Gauthier. "What is new in endothelium-derived hyperpolarizing factors?" Current Opinion in Nephrology and Hypertension 11, no. 2 (2002): 177–83. http://dx.doi.org/10.1097/00041552-200203000-00008.
Full text
5
FARACI, FRANK M., and DONALD D. HEISTAD. "Regulation of the Cerebral Circulation: Role of Endothelium and Potassium Channels." Physiological Reviews 78, no. 1 (1998): 53–97. http://dx.doi.org/10.1152/physrev.1998.78.1.53.
Full textAbstract:
Faraci, Frank M., and Donald D. Heistad. Regulation of the Cerebral Circulation: Role of Endothelium and Potassium Channels. Physiol. Rev. 78: 53–97, 1998. — Several new concepts have emerged in relation to mechanisms that contribute to regulation of the cerebral circulation. This review focuses on some physiological mechanisms of cerebral vasodilatation and alteration of these mechanisms by disease states. One mechanism involves release of vasoactive factors by the endothelium that affect underlying vascular muscle. These factors include endothelium-derived relaxing factor (nitric oxide), prostacyclin, and endothelium-derived hyperpolarizing factor(s). The normal vasodilator influence of endothelium is impaired by some disease states. Under pathophysiological conditions, endothelium may produce potent contracting factors such as endothelin. Another major mechanism of regulation of cerebral vascular tone relates to potassium channels. Activation of potassium channels appears to mediate relaxation of cerebral vessels to diverse stimuli including receptor-mediated agonists, intracellular second messengers, and hypoxia. Endothelial- and potassium channel-based mechanisms are related because several endothelium-derived factors produce relaxation by activation of potassium channels. The influence of potassium channels may be altered by disease states including chronic hypertension, subarachnoid hemorrhage, and diabetes.
6
Baskakov, M. B., and M. S. Yusubov. "Gas attack or gently, the gases!" Bulletin of Siberian Medicine 9, no. 6 (2010): 160–64. http://dx.doi.org/10.20538/1682-0363-2010-6-160-164.
Full textAbstract:
The article contains the current understanding of gas communication in smooth muscle cells, the basic mechanisms of action of gaseous transmitters, analyzes the different views on the nature of the endothelial relaxing and endothelial hyperpolarizing factors. We discuss the controversial issues of the mechanisms of endothelium-dependent relaxation of vascular smooth muscle.
7
McGuire, John J., Hong Ding, and Chris R. Triggle. "Endothelium-derived relaxing factors: A focus on endothelium-derived hyperpolarizing factor(s)." Canadian Journal of Physiology and Pharmacology 79, no. 6 (2001): 443–70. http://dx.doi.org/10.1139/y01-025.
Full textAbstract:
Endothelium-derived hyperpolarizing factor (EDHF) is defined as the non-nitric oxide (NO) and non-prostacyclin (PGI2) substance that mediates endothelium-dependent hyperpolarization (EDH) of vascular smooth muscle cells (VSMC). Although both NO and PGI2 have been demonstrated to hyperpolarize VSMC by cGMP- and cAMP-dependent mechanisms, respectively, and in the case of NO by cGMP-independent mechanisms, a considerable body of evidence suggests that an additional cellular mechanism must exist that mediates EDH. Despite intensive investigation, there is no agreement as to the nature of the cellular processes that mediates the non-NO/PGI2 mediated hyperpolarization. Epoxyeicosatrienoic acids (EET), an endogenous anandamide, a small increase in the extracellular concentration of K+, and electronic coupling via myoendothelial cell gap junctions have all been hypothesized as contributors to EDH. An attractive hypothesis is that EDH is mediated via both chemical and electrical transmissions, however, the contribution from chemical mediators versus electrical transmission varies in a tissue- and species-dependent manner, suggesting vessel-specific specialization. If this hypothesis proves to be correct then the potential exists for the development of vessel and organ-selective vasodilators. Because endothelium-dependent vasodilatation is dysfunctional in disease states (i.e., atherosclerosis), selective vasodilators may prove to be important therapeutic agents.Key words: endothelium, nitric oxide, potassium channels, hyperpolarization, gap junctions.
8
Campbell, William B., Debebe Gebremedhin, Phillip F. Pratt, and David R. Harder. "Identification of Epoxyeicosatrienoic Acids as Endothelium-Derived Hyperpolarizing Factors." Circulation Research 78, no. 3 (1996): 415–23. http://dx.doi.org/10.1161/01.res.78.3.415.
Full text
9
Khalil, Raouf A., and Joey P. Granger. "Vascular mechanisms of increased arterial pressure in preeclampsia: lessons from animal models." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 283, no. 1 (2002): R29—R45. http://dx.doi.org/10.1152/ajpregu.00762.2001.
Full textAbstract:
Normal pregnancy is associated with reductions in total vascular resistance and arterial pressure possibly due to enhanced endothelium-dependent vascular relaxation and decreased vascular reactivity to vasoconstrictor agonists. These beneficial hemodynamic and vascular changes do not occur in women who develop preeclampsia; instead, severe increases in vascular resistance and arterial pressure are observed. Although preeclampsia represents a major cause of maternal and fetal morbidity and mortality, the vascular and cellular mechanisms underlying this disorder have not been clearly identified. Studies in hypertensive pregnant women and experimental animal models suggested that reduction in uteroplacental perfusion pressure and the ensuing placental ischemia/hypoxia during late pregnancy may trigger the release of placental factors that initiate a cascade of cellular and molecular events leading to endothelial and vascular smooth muscle cell dysfunction and thereby increased vascular resistance and arterial pressure. The reduction in uterine perfusion pressure and the ensuing placental ischemia are possibly caused by inadequate cytotrophoblast invasion of the uterine spiral arteries. Placental ischemia may promote the release of a variety of biologically active factors, including cytokines such as tumor necrosis factor-α and reactive oxygen species. Threshold increases in the plasma levels of placental factors may lead to endothelial cell dysfunction, alterations in the release of vasodilator substances such as nitric oxide (NO), prostacyclin (PGI2), and endothelium-derived hyperpolarizing factor, and thereby reductions of the NO-cGMP, PGI2-cAMP, and hyperpolarizing factor vascular relaxation pathways. The placental factors may also increase the release of or the vascular reactivity to endothelium-derived contracting factors such as endothelin, thromboxane, and ANG II. These contracting factors could increase intracellular Ca2+concentrations ([Ca2+]i) and stimulate Ca2+-dependent contraction pathways in vascular smooth muscle. The contracting factors could also increase the activity of vascular protein kinases such as protein kinase C, leading to increased myofilament force sensitivity to [Ca2+]i and enhancement of smooth muscle contraction. The decreased endothelium-dependent mechanisms of vascular relaxation and the enhanced mechanisms of vascular smooth muscle contraction represent plausible causes of the increased vascular resistance and arterial pressure associated with preeclampsia.
10
Villar, Inmaculada C., Adrian J. Hobbs, and Amrita Ahluwalia. "Sex differences in vascular function: implication of endothelium-derived hyperpolarizing factor." Journal of Endocrinology 197, no. 3 (2008): 447–62. http://dx.doi.org/10.1677/joe-08-0070.
Full textAbstract:
The vascular endothelium plays a crucial role in the regulation of vascular homeostasis by controlling vascular tone, coagulation, and inflammatory responses. These actions are exerted by endothelial factors including nitric oxide, prostacyclin, and endothelium-derived hyperpolarizing factor (EDHF). The greater incidence of cardiovascular disease (CVD) in men and postmenopausal women compared with premenopausal women implies a vasoprotective phenotype of females, which may be influenced by sex hormones. These hormones, particularly estrogen, have modulatory effects on the endothelium and circulating cells that have been implicated in vascular inflammation and in the development of CVD. EDHF seems to be the predominant endothelial factor in the resistance vasculature of females and this mediator could afford the beneficial cardiovascular risk profile observed in premenopausal woman. In this review, we discuss sex differences in EDHF biology and how sex hormones can modulate EDHF responses. We also review the implication of sex hormone-dependent regulation of EDHF in inflammatory processes, platelet function, and repair after vascular damage, each of which have a critical role in several aspects of the pathogenesis of CVD.
11
Rossoni, Luciana V., Mercedes Salaices, Marta Miguel, et al. "Ouabain-induced hypertension is accompanied by increases in endothelial vasodilator factors." American Journal of Physiology-Heart and Circulatory Physiology 283, no. 5 (2002): H2110—H2118. http://dx.doi.org/10.1152/ajpheart.00454.2002.
Full textAbstract:
The involvement of nitric oxide (NO), prostaglandins, and calcium-dependent potassium channel (KCa) activators on the negative modulation of phenylephrine-induced contractions was evaluated on the isolated aorta and caudal (CAU) artery obtained from rats treated with ouabain for 5 wk to induce hypertension. In ouabain-treated rats, the reactivity to phenylephrine was reduced in the endothelium-intact aorta but not the CAU segments. Endothelial modulation of phenylephrine contraction, as demonstrated by endothelium removal, NO synthase (NOS) inhibition with N ω-nitro-l-arginine methyl ester and aminoguanidine, as well as KCa inhibition with tetraethylammonium, was more pronounced in segments from ouabain-treated animals, and here greater effects were seen in the aorta than in CAU. An increased expression of endothelial NOS and neuronal NOS was seen in the aorta after ouabain treatment. In CAU, only endothelial NOS was detected and ouabain treatment did not alter its expression. These results suggest that ouabain-induced hypertension is accompanied by increased NO release derived from endothelial NOS and neuronal NOS and increased release of an endothelial hyperpolarizing factor that presumably opens KCa, all of which contribute to the increased negative modulation of the phenylephrine contraction.
12
Craighead, Daniel H., Christian C. Conlon, and Lacy M. Alexander. "Ilex Increases Cutaneous Blood Flow by Augmenting Endothelium-Derived Hyperpolarizing Factors." Medicine & Science in Sports & Exercise 46 (May 2014): 861. http://dx.doi.org/10.1249/01.mss.0000496084.87972.92.
Full text
13
Vanheel, Bert, Patrick Calders, Isabelle Van den Bossche, and Johan Van de Voorde. "Influence of some phospholipase A2 and cytochrome P450 inhibitors on rat arterial smooth muscle K+ currents." Canadian Journal of Physiology and Pharmacology 77, no. 7 (1999): 481–89. http://dx.doi.org/10.1139/y99-050.
Full textAbstract:
The hyperpolarizing factor that is liberated by vascular endothelial cells in response to various agonists, and known to induce relaxation by opening of smooth muscle K+ channels, has been suggested to be a product of cytochrome P450 dependent arachidonic acid metabolism. In this study, the direct influence of two phospholipase A2 inhibitors and of five structurally and mechanistically different cytochrome P450 inhibitors on K+ currents in freshly isolated vascular smooth muscle cells from the rat aorta was investigated. On stepping the cell membrane potential from -70 mV to a series of depolarized test potentials, a noisy outward current developed at test potentials > +10 mV, which showed no appreciable inactivation during the voltage pulse. It was largely abolished by 3 mM external tetraethylammonium chloride (TEA), suggesting that it predominantly consisted of current through large-conductance Ca2+-activated K+ channels. The phospholipase A2 inhibitor quinacrine considerably inhibited this TEA-sensitive current, while 4-bromophenacylbromide exerted no effect. The cytochrome P450 inhibitors proadifen and miconazole reversibly decreased the amplitude of IK, while clotrimazole and 1-aminobenzotriazole had no effect. Conversely, 17-octadecynoic acid increased whole-cell IK. These results show that some phospholipase A2 and cytochrome P450 inhibitors may interfere with K+ channel activation in the rat arterial smooth muscle cell. The relevance of these findings to studies on the involvement of cytochrome P450 dependent metabolism in the generation of the endothelium-derived hyperpolarizing factor in intact arteries is discussed.Key words: endothelial factors, smooth muscle, membrane currents, vasodilation, endothelium-derived hyperpolarizing factor (EDHF), arachidonic acid.
14
Brutsaert, Dirk L. "Cardiac Endothelial-Myocardial Signaling: Its Role in Cardiac Growth, Contractile Performance, and Rhythmicity." Physiological Reviews 83, no. 1 (2003): 59–115. http://dx.doi.org/10.1152/physrev.00017.2002.
Full textAbstract:
Experimental work during the past 15 years has demonstrated that endothelial cells in the heart play an obligatory role in regulating and maintaining cardiac function, in particular, at the endocardium and in the myocardial capillaries where endothelial cells directly interact with adjacent cardiomyocytes. The emerging field of targeted gene manipulation has led to the contention that cardiac endothelial-cardiomyocytal interaction is a prerequisite for normal cardiac development and growth. Some of the molecular mechanisms and cellular signals governing this interaction, such as neuregulin, vascular endothelial growth factor, and angiopoietin, continue to maintain phenotype and survival of cardiomyocytes in the adult heart. Cardiac endothelial cells, like vascular endothelial cells, also express and release a variety of auto- and paracrine agents, such as nitric oxide, endothelin, prostaglandin I2, and angiotensin II, which directly influence cardiac metabolism, growth, contractile performance, and rhythmicity of the adult heart. The synthesis, secretion, and, most importantly, the activities of these endothelium-derived substances in the heart are closely linked, interrelated, and interactive. It may therefore be simplistic to try and define their properties independently from one another. Moreover, in relation specifically to the endocardial endothelium, an active transendothelial physicochemical gradient for various ions, or blood-heart barrier, has been demonstrated. Linkage of this blood-heart barrier to the various other endothelium-mediated signaling pathways or to the putative vascular endothelium-derived hyperpolarizing factors remains to be determined. At the early stages of cardiac failure, all major cardiovascular risk factors may cause cardiac endothelial activation as an adaptive response often followed by cardiac endothelial dysfunction. Because of the interdependency of all endothelial signaling pathways, activation or disturbance of any will necessarily affect the others leading to a disturbance of their normal balance, leading to further progression of cardiac failure.
15
Liu, Qiang, and J. T. Sylvester. "Development of intrinsic tone in isolated pulmonary arterioles." American Journal of Physiology-Lung Cellular and Molecular Physiology 276, no. 5 (1999): L805—L813. http://dx.doi.org/10.1152/ajplung.1999.276.5.l805.
Full textAbstract:
In isolated porcine pulmonary arterioles with endothelium, intraluminal diameter measured at a transmural pressure of 20 mmHg decreased spontaneously from 233 ± 11 to 171 ± 12 μm in 135 min. This intrinsic constriction was not prevented by indomethacin, tetraethylammonium, or superoxide dismutase. Indomethacin plus N G-nitro-l-arginine methyl ester caused initial constriction and BQ-123 or BQ-123 plus BQ-788 caused initial dilation, but these treatments did not prevent subsequent progressive constriction. In pulmonary arterioles with endothelium exposed to calcium-free conditions and pulmonary arterioles without endothelium, the intraluminal diameter measured at a transmural pressure of 20 mmHg was constant at 239 ± 16 and 174 ± 7 μm, respectively. Thus the spontaneous development of tone in isolated pulmonary arterioles required extracellular calcium and resulted from 1) time-independent smooth muscle contraction caused by mechanisms intrinsic to smooth muscle and 2) time-dependent contraction caused by decreasing activity of endothelium-derived relaxing factors other than nitric oxide, vasodilator prostaglandins, and hyperpolarizing factors acting on calcium-dependent potassium channels or increasing activity of endothelium-derived contracting factors other than endothelin-1, vasoconstrictor prostaglandins, and superoxide anions. Further investigation is indicated to identify these unknown mechanisms and determine their role in pulmonary vasoreactivity.
16
Gonzales, Rayna J., Diana N. Krause, and Sue P. Duckles. "Testosterone suppresses endothelium-dependent dilation of rat middle cerebral arteries." American Journal of Physiology-Heart and Circulatory Physiology 286, no. 2 (2004): H552—H560. http://dx.doi.org/10.1152/ajpheart.00663.2003.
Full textAbstract:
Little is known about vascular effects of testosterone. We previously reported chronic testosterone treatment increases vascular tone in middle cerebral arteries (MCA; 300 μm diameter) of male rats. In the present study, we investigated the hypothesis that physiological levels of circulating testosterone affect endothelial factors that modulate cerebrovascular reactivity. Small branches of MCA (150 μm diameter) were isolated from orchiectomized (ORX) and testosterone-treated (ORX+T) rats. Intraluminal diameters were recorded after step changes in intraluminal pressure (20–100 Torr) in the absence or presence of NG-nitro-l-arginine-methyl ester (l-NAME), a nitric oxide synthase (NOS) inhibitor; indomethacin, a cyclooxygenase (COX) inhibitor; and/or apamin and charybdotoxin (CTX); and KCa channel blockers used to inhibit endothelium-derived hyperpolarizing factors (EDHF). At intraluminal pressures ≥60 Torr, arteries from ORX+T developed greater tone compared with ORX arteries. This difference was abolished by removal of the endothelium but remained after treatment of intact arteries with indomethacin or l-NAME. In addition, testosterone treatment had no effect on cerebrovascular production of endothelin-1 or prostacyclin nor did it alter protein levels of endothelial NOS or COX-1. Endothelium removal after l-NAME/indomethacin exposure caused an additional increase in tone. Interestingly, the latter effect was smaller in arteries from ORX+T, suggesting testosterone affects endothelial vasodilators that are independent of NOS and COX. Apamin/CTX, in the presence of l-NAME/indomethacin, abolished the difference in tone between ORX and ORX+T and resulted in vessel diameters similar to those of endothelium-denuded preparations. In conclusion, testosterone may modulate vascular tone in cerebral arteries by suppressing EDHF.
17
Kuroiwa, Mari, Junji Nishimura, and Hideo Kanaide. "Substance P relaxes pig coronary artery through endothelium-derived relaxing and hyperpolarizing factors." Japanese Journal of Pharmacology 61 (1993): 218. http://dx.doi.org/10.1016/s0021-5198(19)51744-9.
Full text
18
Kopf, Phillip G., David X. Zhang, Kathryn M. Gauthier, et al. "Adrenic Acid Metabolites as Endogenous Endothelium-Derived and Zona Glomerulosa-Derived Hyperpolarizing Factors." Hypertension 55, no. 2 (2010): 547–54. http://dx.doi.org/10.1161/hypertensionaha.109.144147.
Full text
19
Herman, Arnold G., and Paul M. Vanhoutte. "9th International Symposium on Mechanisms of Vasodilatation and Endothelium-Derived Hyperpolarizing Factors (EDHF)." Journal of Vascular Research 42, no. 1 (2005): 1–90. http://dx.doi.org/10.1159/000086311.
Full text
20
Petterson, Jennifer L., Myles W. O’Brien, Jarrett A. Johns, Jack Chiasson, and Derek S. Kimmerly. "Influence of prostaglandins and endothelial-derived hyperpolarizing factors on brachial and popliteal endothelial-dependent function in young adults." Journal of Applied Physiology 130, no. 1 (2021): 17–25. http://dx.doi.org/10.1152/japplphysiol.00698.2020.
Full textAbstract:
We compared changes in upper- and lower-limb artery endothelial-dependent vasodilatory and vasoconstrictor responses between control, prostaglandin inhibition, and endothelial-derived hyperpolarizing factor inhibition conditions. Neither prostaglandins nor endothelial-derived hyperpolarizing factor influenced flow-mediated dilation responses in either the brachial or popliteal artery. In contrast, endothelial-derived hyperpolarizing factor, but not prostaglandins, reduced resting brachial artery blood flow and shear rate and resting popliteal artery diameter, as well as low-flow-mediated constriction responses in both the popliteal and brachial arteries.
21
Zhang, Yongde, Christine L. Oltman, Tong Lu, Hon-Chi Lee, Kevin C. Dellsperger, and Mike VanRollins. "EET homologs potently dilate coronary microvessels and activate BKCa channels." American Journal of Physiology-Heart and Circulatory Physiology 280, no. 6 (2001): H2430—H2440. http://dx.doi.org/10.1152/ajpheart.2001.280.6.h2430.
Full textAbstract:
Epoxyeicosatrienoic acids (EETs) are released from endothelial cells and potently dilate small arteries by hyperpolarizing vascular myocytes. In the present study, we investigated the structural specificity of EETs in dilating canine and porcine coronary microvessels (50–140 μm ID) and activating large-conductance Ca2+-activated K+(BKCa) channels. The potencies and efficacies of EET regioisomers and enantiomers were compared with those of two EET homologs: epoxyeicosaquatraenoic acids (EEQs), which are made from eicosapentaenoic acid by the same cytochrome P-450 epoxygenase that generates EETs from arachidonic acid, and epoxydocosatetraenoic acids (EDTs), which are EETs that are two carbons longer. With EC50 values of 3–120 pM but without regio- or stereoselectivity, EETs potently dilated canine and porcine microvessels. Surprisingly, the EEQs and EDTs had comparable potencies and efficacies in dilating microvessels. Moreover, 50 nM 13,14-EDT activated the BKCa channels with the same efficacy as either 11,12-EET enantiomer at 50 nM. We conclude that coronary microvessels and BKCa channels possess low structural specificity for EETs and suggest that EEQs and EDTs may thereby also be endothelium-derived hyperpolarizing factors.
22
Haji, Abdulsatar A., and Omar A. M. Al-Habib. "The Role of K+, Ca2+ channels, Some Endothelium Hyperpolarizing Factors in Taurine Induced Vasorelaxation in Rats Aorta." Technium BioChemMed 2, no. 1 (2021): 101–9. http://dx.doi.org/10.47577/biochemmed.v2i1.3234.
Full textAbstract:
The current study included the relaxant effect of taurine on rat’s aortic rings and the mechanism behind this relaxation. Taurine produced a potent spasmolytic effect on aortic rings at concentrations from zero to 80 mM. The results of K+ channel subtypes using specific blockers indicated that the Kv channel has a considerable role in taurine-induced relaxation, while KATP has a limited role, Exposure of aortic rings to combinations of two K+ blockers showed that KCa, Kv, and KIR play important role in taurine mediated relaxation. The endothelium-derived hyperpolarizing factors used showed responses to a variable extent in taurine mediated relaxation; since NO and cGMP played a major role whereas PGS played a minor role in taurine mediated relaxation. Finally, the results also indicated that taurine-mediated relaxation is endothelium-dependent.
23
Bellien, Jeremy, Christian Thuillez, and Robinson Joannides. "Contribution of endothelium-derived hyperpolarizing factors to the regulation of vascular tone in humans." Fundamental & Clinical Pharmacology 22, no. 4 (2008): 363–77. http://dx.doi.org/10.1111/j.1472-8206.2008.00610.x.
Full text
24
Sandhya, Badoni *. Arun Kumar Aarti Sati. "A REVIEW ARTICLE ON ENDOTHELIAL DYSFUNCTION IN PATIENT WITH TYPE 2 DIABETES MELLITUS." INDO AMERICAN JOURNAL OF PHARMACEUTICAL SCIENCES 05, no. 02 (2018): 1102–14. https://doi.org/10.5281/zenodo.1188219.
Full textAbstract:
The endothelial cells involved in modulating vascular tone and structure. Endothelial cells produce a vast range of causes that also regulate cellular adhesion, smooth muscle proliferations and vessel wall inflammation. Endothelial function is important for homeostasis of the body and its dysfunction is associated with several pathophysiology conditions like diabetes, atherosclerosis. Sufferers with diabetes at all times exhibit an impairment of endotheliumdependent vasodilation. Therefore, working out and treating endothelial dysfunction is the principle focus within the prevention of vascular problems associated with all types of diabetes mellitus. This review will focus on the pathophysiology, assessment and therapeutics that exceptionally target endothelial dysfunction within the context of diabetic setting. Pathophysiology including nitric oxide, oxidative stress, angII, diabetes will be discussed. Pharmacological approaches that upregulate endothelium derives nitric oxide synthase and treatment that might prevent the development of diabetes associated vascular complications will be discussed. Keywords: endothelial dysfunction, nitric oxide, nitric oxide synthase ,vascular smooth muscle cells, endothelialderived hyperpolarizing factors.
25
Bashir, Thamer M., and Omar A. M. Al-Habib. "The Role of K+, Ca2+ channels and Endothelial Hyperpolarizing Factors in Vasorelaxation Induced by Tribulus terrestris." Technium BioChemMed 2, no. 1 (2021): 94–100. http://dx.doi.org/10.47577/biochemmed.v2i1.3233.
Full textAbstract:
The present study focused on the relaxant effect of themethanolic extract (ME) of Tribulus terristris on rats’ thoracic aortae and included the study of underlying vasorelaxation mechanisms. The methanolic extract produced concentration-dependent relaxation in rats’ aorta. The methanolic extract produced concentration-dependent relaxation in the aortic rings. The use of different K+ channel blockers (BaCl2, 4-AP, GLIB, and TEA) indicated that Kv, KATP, KIR, and KCa and L-type Ca channels played no role in the methanolic extractinduced relaxation. However, with respect to endothelium-derived hyperpolarizing factors, PGI2 and sGC produced a mild inhibition in the relaxation response to ME while NO produced no effect at all.
 Based on the novel results of the current study, it can be concluded that T. terrestris methanolic extract (ME) mediated relaxation in isolated rat aortic tissues in a concentration-dependent manner. Moreover, we discovered that ME-mediated relaxation is endothelium-dependent and that potassium and calcium ion channels play no role in this relaxation with a limited role of PGI2 and sGC.
26
Takaki, Aya, Keiko Morikawa, Masato Tsutsui, et al. "Crucial role of nitric oxide synthases system in endothelium-dependent hyperpolarization in mice." Journal of Experimental Medicine 205, no. 9 (2008): 2053–63. http://dx.doi.org/10.1084/jem.20080106.
Full textAbstract:
The endothelium plays an important role in maintaining vascular homeostasis by synthesizing and releasing several relaxing factors, such as prostacyclin, nitric oxide (NO), and endothelium-derived hyperpolarizing factor (EDHF). We have previously demonstrated in animals and humans that endothelium-derived hydrogen peroxide (H2O2) is an EDHF that is produced in part by endothelial NO synthase (eNOS). In this study, we show that genetic disruption of all three NOS isoforms (neuronal [nNOS], inducible [iNOS], and endothelial [eNOS]) abolishes EDHF responses in mice. The contribution of the NOS system to EDHF-mediated responses was examined in eNOS−/−, n/eNOS−/−, and n/i/eNOS−/− mice. EDHF-mediated relaxation and hyperpolarization in response to acetylcholine of mesenteric arteries were progressively reduced as the number of disrupted NOS genes increased, whereas vascular smooth muscle function was preserved. Loss of eNOS expression alone was compensated for by other NOS genes, and endothelial cell production of H2O2 and EDHF-mediated responses were completely absent in n/i/eNOS−/− mice, even after antihypertensive treatment with hydralazine. NOS uncoupling was not involved, as modulation of tetrahydrobiopterin (BH4) synthesis had no effect on EDHF-mediated relaxation, and the BH4/dihydrobiopterin (BH2) ratio was comparable in mesenteric arteries and the aorta. These results provide the first evidence that EDHF-mediated responses are dependent on the NOSs system in mouse mesenteric arteries.
27
Chawengsub, Yuttana, Kathryn M. Gauthier, and William B. Campbell. "Role of arachidonic acid lipoxygenase metabolites in the regulation of vascular tone." American Journal of Physiology-Heart and Circulatory Physiology 297, no. 2 (2009): H495—H507. http://dx.doi.org/10.1152/ajpheart.00349.2009.
Full textAbstract:
Stimulation of vascular endothelial cells with agonists such as acetylcholine (ACh) or bradykinin or with shear stress activates phospholipases and releases arachidonic acid (AA). AA is metabolized by cyclooxygenases, cytochrome P-450s, and lipoxygenases (LOs) to vasoactive products. In some arteries, a substantial component of the vasodilator response is dependent on LO metabolites of AA. Nitric oxide (NO)- and prostaglandin (PG)-independent vasodilatory responses to ACh and AA are reduced by inhibitors of LO and by antisense oligonucleotides specifically against 15-LO-1. Vasoactive 15-LO metabolites derived from the vascular endothelium include 15-hydroxy-11,12-epoxyeicosatrienoic acid (15-H-11,12-HEETA) that is hydrolyzed by soluble epoxide hydrolase to 11,12,15-trihydroxyeicosatrienoic acid (11,12,15-THETA). HEETA and THETA are endothelium-derived hyperpolarizing factors that induce vascular relaxations by activation of smooth muscle apamin-sensitive, calcium-activated, small-conductance K+ channels causing hyperpolarization. In other arteries, the 12-LO metabolite 12-hydroxyeicosatetraenoic acid is synthesized by the vascular endothelium and relaxes smooth muscle by large-conductance, calcium-activated K+ channel activation. Thus formation of vasodilator eicosanoids derived from LO pathways contributes to the regulation of vascular tone, local blood flow, and blood pressure.
28
Moretti, Rita, and Paola Caruso. "Small Vessel Disease: Ancient Description, Novel Biomarkers." International Journal of Molecular Sciences 23, no. 7 (2022): 3508. http://dx.doi.org/10.3390/ijms23073508.
Full textAbstract:
Small vessel disease (SVD) is one of the most frequent pathological conditions which lead to dementia. Biochemical and neuroimaging might help correctly identify the clinical diagnosis of this relevant brain disease. The microvascular alterations which underlie SVD have common origins, similar cognitive outcomes, and common vascular risk factors. Nevertheless, the arteriolosclerosis process, which underlines SVD development, is based on different mechanisms, not all completely understood, which start from a chronic hypoperfusion state and pass through a chronic brain inflammatory condition, inducing a significant endothelium activation and a consequent tissue remodeling action. In a recent review, we focused on the pathophysiology of SVD, which is complex, involving genetic conditions and different co-morbidities (i.e., diabetes, chronic hypoxia condition, and obesity). Currently, many points still remain unclear and discordant. In this paper, we wanted to focus on new biomarkers, which can be the expression of the endothelial dysfunction, or of the oxidative damage, which could be employed as markers of disease progression or for future targets of therapies. Therefore, we described the altered response to the endothelium-derived nitric oxide-vasodilators (ENOV), prostacyclin, C-reactive proteins, and endothelium-derived hyperpolarizing factors (EDHF). At the same time, due to the concomitant endothelial activation and chronic neuroinflammatory status, we described hypoxia-endothelial-related markers, such as HIF 1 alpha, VEGFR2, and neuroglobin, and MMPs. We also described blood–brain barrier disruption biomarkers and imaging techniques, which can also describe perivascular spaces enlargement and dysfunction. More studies should be necessary, in order to implement these results and give them a clinical benefit.
29
Sunano, S., H. Watanabe, S. Tanaka, F. Sekiguchi, and K. Shimamura. "Endothelium-derived relaxing, contracting and hyperpolarizing factors of mesenteric arteries of hypertensive and normotensive rats." British Journal of Pharmacology 126, no. 3 (1999): 709–16. http://dx.doi.org/10.1038/sj.bjp.0702355.
Full text
30
Matin, Nusrat, Courtney Fisher, William F. Jackson, and Anne M. Dorrance. "Bilateral common carotid artery stenosis in normotensive rats impairs endothelium-dependent dilation of parenchymal arterioles." American Journal of Physiology-Heart and Circulatory Physiology 310, no. 10 (2016): H1321—H1329. http://dx.doi.org/10.1152/ajpheart.00890.2015.
Full textAbstract:
Chronic cerebral hypoperfusion is a risk factor for cognitive impairment. Reduced blood flow through the common carotid arteries induced by bilateral carotid artery stenosis (BCAS) is a physiologically relevant model of chronic cerebral hypoperfusion. We hypothesized that BCAS in 20-wk-old Wistar-Kyoto (WKY) rats would impair cognitive function and lead to reduced endothelium-dependent dilation and outward remodeling in the parenchymal arterioles (PAs). After 8 wk of BCAS, both short-term memory and spatial discrimination abilities were impaired. In vivo assessment of cerebrovascular reserve capacity showed a severe impairment after BCAS. PA endothelial function and structure were assessed by pressure myography. BCAS impaired endothelial function in PAs, as evidenced by reduced dilation to carbachol. Addition of nitric oxide synthase and cyclooxygenase inhibitors did not change carbachol-mediated dilation in either group. Inhibiting CYP epoxygenase, the enzyme that produces epoxyeicosatrienoic acid (EETs), a key determinant of endothelium-derived hyperpolarizing factor (EDHF)-mediated dilation, abolished dilation in PAs from Sham rats, but had no effect in PAs from BCAS rats. Expression of TRPV4 channels, a target for EETs, was decreased and maximal dilation to a TRPV4 agonist was attenuated after BCAS. Together these data suggest that EET-mediated dilation is impaired in PAs after BCAS. Thus impaired endothelium-dependent dilation in the PAs may be one of the contributing factors to the cognitive impairment observed after BCAS.
31
Akata, Takashi, Mikio Nakashima, Kenji Kodama, Walter A. Boyle, and Shosuke Takahashi. "Effects of Volatile Anesthetics on Acetylcholine-induced Relaxation in the Rabbit Mesenteric Resistance Artery." Anesthesiology 82, no. 1 (1995): 188–204. http://dx.doi.org/10.1097/00000542-199501000-00024.
Full textAbstract:
Background Vascular endothelium plays an important role in the regulation of vascular tone. Volatile anesthetics have been shown to attenuate endothelium-mediated relaxation in conductance arteries, such as aorta. However, significant differences in volatile anesthetic pharmacology between these large vessels and the small vessels that regulate systemic vascular resistance and blood flow have been documented, yet little is known about volatile anesthetic action on endothelial function in resistance arteries. Furthermore, endothelium-dependent relaxation mediated by factors other than endothelium-derived relaxing factor (EDRF) has recently been recognized, and there is no information available regarding volatile anesthetic action on non-EDRF-mediated endothelium-dependent relaxation. Methods Employing isometric tension recording and microelectrode methods, the authors first characterized the endothelium-dependent relaxing and hyperpolarizing actions of acetylcholine (ACh) in rabbit small mesenteric arteries, and tested the sensitivities of these actions to EDRF pathway inhibitors and K+ channel blockers. They then examined the effects of the volatile anesthetics isoflurane, enflurane, and sevoflurane on ACh-induced endothelium-dependent relaxation that was sensitive to EDRF inhibitors and that which was resistant to the EDRF inhibitors but sensitive to blockers of ACh-induced hyperpolarization. The effects of the volatile anesthetics on endothelium-independent sodium nitroprusside (SNP)-induced relaxation were also studied. Results Acetylcholine concentration-dependently caused both endothelium-dependent relaxation and hyperpolarization of vascular smooth muscle. The relaxation elicited by low concentrations of ACh (< or = 0.1 microM) was almost completely abolished by the EDRF inhibitors NG-nitro-L-arginine (LNNA), oxyhemoglobin (HbO2), and methylene blue (MB). The relaxation elicited by higher concentrations of ACh (> or = 0.3 microM) was only attenuated by the EDRF inhibitors. The remaining relaxation, as well as the ACh-induced hyperpolarization that was also resistant to EDRF inhibitors, were both specifically blocked by tetraethylammonium (TEA > or = 10 mM). Sodium nitroprusside, a NO donor, produced dose-dependent relaxation, but not hyperpolarization, in the endothelium-denuded (E[-]) strips, and the relaxation was inhibited by MB and HbO2, but not TEA (> or = 10 mM). One MAC isoflurane, enflurane, and sevoflurane inhibited both ACh relaxation that was sensitive to the EDRF inhibitors and the ACh relaxation resistant to the EDRF inhibitors and sensitive to TEA, but not SNP relaxation (in the E[-] strips). An additional finding was that the anesthetics all significantly inhibited norepinephrine (NE) contractions in the presence and absence of the endothelium or after exposure to the EDRF inhibitors. Conclusions The results confirm that ACh has a hyperpolarizing action in rabbit small mesenteric resistance arteries that is independent of EDRF inhibitors but blocked by the K+ channel blocker TEA. The ACh relaxation in these resistance arteries thus appears to consist of distinct EDRF-mediated and hyperpolarization-mediated components. Isoflurane, enflurane, and sevoflurane inhibited both components of the ACh-induced relaxation in these small arteries, indicating a more global depression of endothelial function or ACh signaling in endothelial cells, rather than a specific effect on the EDRF pathway. All these anesthetics exerted vasodilating action in the presence of NE, the primary neurotransmitter of the sympathetic nervous system, which plays a major role in maintaining vasomotor tone in vivo. This strongly indicates that the vasodilating action of these anesthetics probably dominates over their inhibitory action on the EDRF pathway and, presumably, contributes to their known hypotensive effects in vivo. Finally, the vasodilating action of these anesthetics is, at least in part, independent from endothelium.
32
Okazaki, Kayoko, Sumihiko Seki, Noriaki Kanaya, Jun-ichi Hattori, Noritsugu Tohse, and Akiyoshi Namiki. "Role of Endothelium-derived Hyperpolarizing Factor in Phenylephrine-induced Oscillatory Vasomotion in Rat Small Mesenteric Artery." Anesthesiology 98, no. 5 (2003): 1164–71. http://dx.doi.org/10.1097/00000542-200305000-00019.
Full textAbstract:
Background In small mesenteric arteries, endothelium-derived hyperpolarizing factor (EDHF) in addition to endothelium-derived relaxing factors (EDRFs) including NO plays an important role in acetylcholine-induced vasodilation. It has been reported that EDRFs play an important role in alpha(1)-adrenoceptor agonist-induced oscillatory vasomotion and in limiting vasoconstrictor response to the agonists; however, contribution of EDHF to the alpha(1)-agonist-induced oscillation is unknown. Methods Rat small mesenteric arteries were isolated and cannulated at each end with a glass micropipette. The vessels were immersed in a bath (37 degrees C) containing physiologic saline solution. Changes in vessel diameter were measured using an optical density video detection system. Results Denudation of the endothelium and inhibition of NO synthesis caused a leftward shift in the concentration-response relation for phenylephrine in the mesenteric arteries, whereas inhibition of cyclooxygenase by indomethacin had no effect. Blockade of Ca2+-activated K+ (K(Ca)) channels by charybdotoxin and apamin caused a further leftward shift in the concentration-response relation in the vessels pretreated with Nomega-nitro-l-arginine methylester and indomethacin. Phenylephrine at concentrations higher than 10(-6) m caused endothelium-dependent oscillatory vasomotion, which was reduced but not abolished after combined inhibition of the cyclooxygenase and NO synthase pathways. However, the K(Ca) channel blockers completely abolished the remaining component of oscillation. Conclusions Endothelially-derived NO is an important modulator of sustained agonist-induced vasoconstriction. NO, as well as endothelially-derived cyclooxygenase products and EDHF, also contribute significantly to phenylephrine-induced oscillatory vasomotion.
33
Zhang, Hanrui, Yoonjung Park, Junxi Wu та ін. "Role of TNF-α in vascular dysfunction". Clinical Science 116, № 3 (2009): 219–30. http://dx.doi.org/10.1042/cs20080196.
Full textAbstract:
Healthy vascular function is primarily regulated by several factors including EDRF (endothelium-dependent relaxing factor), EDCF (endothelium-dependent contracting factor) and EDHF (endothelium-dependent hyperpolarizing factor). Vascular dysfunction or injury induced by aging, smoking, inflammation, trauma, hyperlipidaemia and hyperglycaemia are among a myriad of risk factors that may contribute to the pathogenesis of many cardiovascular diseases, such as hypertension, diabetes and atherosclerosis. However, the exact mechanisms underlying the impaired vascular activity remain unresolved and there is no current scientific consensus. Accumulating evidence suggests that the inflammatory cytokine TNF (tumour necrosis factor)-α plays a pivotal role in the disruption of macrovascular and microvascular circulation both in vivo and in vitro. AGEs (advanced glycation end-products)/RAGE (receptor for AGEs), LOX-1 [lectin-like oxidized low-density lipoprotein receptor-1) and NF-κB (nuclear factor κB) signalling play key roles in TNF-α expression through an increase in circulating and/or local vascular TNF-α production. The increase in TNF-α expression induces the production of ROS (reactive oxygen species), resulting in endothelial dysfunction in many pathophysiological conditions. Lipid metabolism, dietary supplements and physical activity affect TNF-α expression. The interaction between TNF-α and stem cells is also important in terms of vascular repair or regeneration. Careful scrutiny of these factors may help elucidate the mechanisms that induce vascular dysfunction. The focus of the present review is to summarize recent evidence showing the role of TNF-α in vascular dysfunction in cardiovascular disease. We believe these findings may prompt new directions for targeting inflammation in future therapies.
34
Jia, Guanghong, William Durante, and James R. Sowers. "Endothelium-Derived Hyperpolarizing Factors: A Potential Therapeutic Target for Vascular Dysfunction in Obesity and Insulin Resistance." Diabetes 65, no. 8 (2016): 2118–20. http://dx.doi.org/10.2337/dbi16-0026.
Full text
35
Lischke, Volker, Rudi Busse, and Markus Hecker. "Inhalation Anesthetics Inhibit the Release of Endothelium-derived Hyperpolarizing Factor in the Rabbit Carotid Artery." Anesthesiology 83, no. 3 (1995): 574–82. http://dx.doi.org/10.1097/00000542-199509000-00017.
Full textAbstract:
Background Inhalation anesthetics may interfere with the synthesis or action of endothelium-derived vasoactive factors. We investigated the effects of desflurane, enflurane, halothane, isoflurane, and sevoflurane on the release of nitric oxide and endothelium-derived hyperpolarizing factor (EDHF) in the isolated endothelium-intact carotid artery of the rabbit. Methods Isolated segments of the carotid artery were suspended in Krebs-Henseleit solution (37 degrees C) and preconstricted with phenylephrine (1 microM). Relaxations caused by acetylcholine (ACh) (0.03-10 microM) or sodium nitroprusside (0.01-10 microM) were compared in the presence or absence of the nitric oxide synthase inhibitor NG-nitro-L-arginine (0.1 mM) in segments exposed to desflurane (8%), enflurane (2-4%), halothane (2-3.5%), isoflurane (2-4%), or sevoflurane (2%) as well as in NG-nitro-L- arginine-treated segments exposed to enflurane (2%) in combination with the KCa(+)-channel blocker tetrabutylammonium (0.3 mM) or the cytochrome P450 inhibitor clotrimazole (3 microM). Results Desflurane, enflurane, and sevoflurane selectively inhibited the ACh-induced release of EDHF. Halothane and isoflurane also weakly affected the nitric oxide-mediated relaxant response to ACh. The inhibitory effect of these two anesthetics on EDHF release was concentration-dependent. Relaxations induced by sodium nitroprusside were not inhibited by any of the anesthetics tested. Three structurally unrelated cytochrome P450 inhibitors clotrimazole (0.1 mM), metyrapone (1 mM), and SKF525a (proadifen, 0.1 mM) abolished the EDHF-mediated relaxation elicited by ACh. The pharmacologic profile of the inhibitory effect of enflurane on the release of EDHF closely resembled that of clotrimazole but not that of tetrabutylammonium. Moreover, all anesthetics inhibited the cytochrome P450-catalyzed O-dealkylation of 7-ethoxycoumarin by rabbit liver microsomes in a concentration-dependent manner. Conclusions Inhalation anesthetics significantly attenuate the EDHF-mediated relaxant response to ACh in the rabbit carotid artery. This effect appears to be attributable to inhibition of the cytochrome P450-dependent synthesis of EDHF by the endothelium.
36
Hein, Travis W., James C. Liao, and Lih Kuo. "oxLDL specifically impairs endothelium-dependent, NO-mediated dilation of coronary arterioles." American Journal of Physiology-Heart and Circulatory Physiology 278, no. 1 (2000): H175—H183. http://dx.doi.org/10.1152/ajpheart.2000.278.1.h175.
Full textAbstract:
Our previous studies implicated that oxidized low-density lipoprotein (oxLDL), a putative atherogenic agent, impairs endothelium-dependent, nitric oxide (NO)-mediated dilation of isolated coronary arterioles to pharmacological agonists. However, it is not known whether oxLDL specifically affects NO-mediated dilation or generally impairs endothelium-dependent function, including the release of hyperpolarizing factors. In this regard, we investigated the dilation of isolated porcine coronary arterioles (50- to 100-μm luminal diameter) in response to the activation of various endothelium-dependent pathways before and after intraluminal incubation of the vessels with oxLDL (0.5 mg protein/ml for 60 min). In the absence of oxLDL, all vessels developed basal tone and dilated in response to the activation of NO synthase (by flow and adenosine), cyclooxygenase (by arachidonic acid), cytochrome P-450 monooxygenase (by bradykinin), and endothelial membrane hyperpolarization (by sucrose-induced hyperosmolarity). Incubation of the vessels with oxLDL for 60 min did not alter basal tone but did inhibit the vasodilatory responses to increased flow and adenosine in a manner similar to that of the NO synthase inhibitor N G-nitro-l-arginine methyl ester. Vasodilations in response to flow and adenosine were not affected by intraluminal incubation of the vessels with either a vehicle solution or the native LDL (0.5 mg protein/ml, 60 min). In contrast with the NO-mediated response, hyperosmotic vasodilation mediated by endothelial hyperpolarization was not affected by oxLDL. Endothelium-dependent dilations to the cyclooxygenase activator arachidonic acid and to the cytochrome P-450 monooxygenase activator bradykinin and endothelium-independent vasodilation to sodium nitroprusside were also not altered by oxLDL. Collectively, these results indicate that oxLDL has a selective effect on endothelium-dependent dilation with specific impairment of the NO-mediated response, whereas cyclooxygenase and cytochrome P-450 monooxygenase-mediated dilations are spared from this inhibitory effect. In addition, oxLDL does not appear to affect vasodilation mediated by hyperpolarization of the endothelium.
37
Tanaka, Mitsuaki, Hiroshi Kanatsuka, Boon-Hooi Ong, et al. "Cytochrome P-450 metabolites but not NO, PGI2, and H2O2 contribute to ACh-induced hyperpolarization of pressurized canine coronary microvessels." American Journal of Physiology-Heart and Circulatory Physiology 285, no. 5 (2003): H1939—H1948. http://dx.doi.org/10.1152/ajpheart.00190.2003.
Full textAbstract:
The endothelium-dependent hyperpolarization of cells has a crucial role in regulating vascular tone, especially in microvessels. Nitric oxide (NO) and prostacyclin (PGI2), in addition to endothelium-derived hyperpolarizing factor (EDHF), have been reported to hyperpolarize vascular smooth muscle in several organs. Studies have reported the hyperpolarizing effects of these factors are increased by a stretch in large coronary arteries. EDHF has not yet been identified and cytochrome P-450 metabolites and H2O2 are candidates for EDHF. With the use of the membrane potential-sensitive fluorescent dye bis-(1,3-dibutylbarbituric acid)trimethione oxonol [DiBAC4(3)], we examined whether NO, PGI2, cytochrome P-450 metabolites, and H2O2 contribute to ACh-induced hyperpolarization in pressurized coronary microvessels. Canine coronary arterial microvessels (60–356 μm internal diameter) were cannulated and pressurized at 60 cmH2O in a vessel chamber perfused with physiological salt solution containing DiBAC4(3). Fluorescence intensity and diameter were measured on a computer. There was a linear correlation between changes in the fluorescence intensity and membrane potential. ACh significantly decreased the fluorescence intensity (hyperpolarization) of the microvessels without any inhibitors. Endothelial damage caused by air perfusion abolished the ACh-induced decrease in fluorescence intensity. The inhibitors of NO synthase and cyclooxygenase did not affect the ACh-induced decreases in the fluorescence intensity. The addition of 17-octadecynoic acid, a cytochrome P-450 monooxygenase inhibitor, to those inhibitors significantly attenuated the ACh-induced decreases in fluorescence intensity, whereas catalase, an enzyme that dismutates H2O2 to form water and oxygen, did not. Furthermore, catalase did not affect the vasodilation produced by ACh. These results indicate that NO and PGI2 do not contribute to the ACh-induced hyperpolarization and that the cytochrome P-450 metabolites but not H2O2 are involved in EDHF-mediated hyperpolarization in canine coronary arterial microvessels.
38
Cracowski, Jean‐Luc, and Matthieu Roustit. "Human Skin Microcirculation." Comprehensive Physiology 10, no. 3 (2020): 1105–54. https://doi.org/10.1002/j.2040-4603.2020.tb00131.x.
Full textAbstract:
AbstractThe anatomy and physiology of the microcirculation in human skin are complex. Normal cutaneous microcirculation is organized in two parallel plexuses with capillary loops extending perpendicularly from the superficial plexus. The physiological regulation of cutaneous microcirculation includes specific sympathetic activation, which causes vasoconstriction through the release of norepinephrine, neuropeptide Y, and ATP. A sympathetic cholinergic system is mainly involved in vasodilation through the co‐transmission of acetylcholine, vasoactive intestinal peptide, and pituitary adenylate cyclase‐activating peptide. Sensory nerves play a major role through the release of calcitonin gene‐related peptide and substance P. Endothelium‐dependent vasomotion implicates nitric oxide, prostacyclin, endothelium‐dependent hyperpolarizing factors, and endothelin. Myogenic response also plays a role and explains why autoregulation is weak but exists in glabrous human skin. Variations in skin blood flow result from highly complex interactions between these mechanisms. In this article, we will detail the anatomy, physiology, and current methods of exploring the human microcirculation. We will further discuss the part played by cutaneous microvascular impairment in the pathophysiology of cardiovascular and metabolic diseases, or diseases more specifically affecting the skin. © 2020 American Physiological Society. Compr Physiol 10:1105‐1154, 2020.
39
Spilk, Samson, Michael D. Herr, Lawrence I. Sinoway, and Urs A. Leuenberger. "Endothelium-derived hyperpolarizing factor contributes to hypoxia-induced skeletal muscle vasodilation in humans." American Journal of Physiology-Heart and Circulatory Physiology 305, no. 11 (2013): H1639—H1645. http://dx.doi.org/10.1152/ajpheart.00073.2013.
Full textAbstract:
Systemic hypoxia causes skeletal muscle vasodilation, thereby preserving O2 delivery to active tissues. Nitric oxide (NO), adenosine, and prostaglandins contribute to this vasodilation, but other factors may also play a role. We tested the hypothesis that regional inhibition of endothelium-derived hyperpolarizing factor with the cytochrome P-450 2C9 antagonist fluconazole, alone or combined with the NO synthase antagonist NG-monomethyl-l-arginine (l-NMMA), attenuates hypoxia-induced vasodilation. We compared forearm blood flow (FBF) and skin blood flow before and during brachial artery infusion of fluconazole (0.3 mg/min; trial 1) or fluconazole + l-NMMA (50 mg over 10 min; trial 2) and during systemic hypoxia (10 min, arterial Po2 ∼37 mmHg) in infused (experimental) and control forearms of 12 healthy humans. During normoxia, fluconazole and fluconazole + l-NMMA reduced ( P < 0.05) forearm vascular conductance (FVC) by ∼10% and ∼18%, respectively. During hypoxia and fluconazole ( trial 1), FVC increased by 1.76 ± 0.37 and 0.95 ± 0.35 units in control and experimental forearms, respectively ( P < 0.05). During hypoxia and fluconazole + l-NMMA ( trial 2), FVC increased by 2.32 ± 0.51 and 0.72 ± 0.22 units in control and experimental forearms, respectively ( P < 0.05). Similarly, during hypoxia with l-NMMA alone ( trial 3; n = 8) FVC increased by 1.51 ± 0.46 and 0.45 ± 0.32 units in control and experimental forearms, respectively ( P < 0.05). These effects were not due to altered skin blood flow. We conclude that endothelium-derived hyperpolarizing factor contributes to basal vascular tone and to hypoxia-induced skeletal muscle vasodilation and could be particularly relevant when other vasodilator systems are impaired.
40
Félétou, Michel, and Paul M. Vanhoutte. "EDHF: an update." Clinical Science 117, no. 4 (2009): 139–55. http://dx.doi.org/10.1042/cs20090096.
Full textAbstract:
The endothelium controls vascular tone not only by releasing NO and prostacyclin, but also by other pathways causing hyperpolarization of the underlying smooth muscle cells. This characteristic was at the origin of the term ‘endothelium-derived hyperpolarizing factor’ (EDHF). However, this acronym includes different mechanisms. Arachidonic acid metabolites derived from the cyclo-oxygenases, lipoxygenases and cytochrome P450 pathways, H2O2, CO, H2S and various peptides can be released by endothelial cells. These factors activate different families of K+ channels and hyperpolarization of the vascular smooth muscle cells contribute to the mechanisms leading to their relaxation. Additionally, another pathway associated with the hyperpolarization of both endothelial and vascular smooth muscle cells contributes also to endothelium-dependent relaxations (EDHF-mediated responses). These responses involve an increase in the intracellular Ca2+ concentration of the endothelial cells, followed by the opening of SKCa and IKCa channels (small and intermediate conductance Ca2+-activated K+ channels respectively). These channels have a distinct subcellular distribution: SKCa are widely distributed over the plasma membrane, whereas IKCa are preferentially expressed in the endothelial projections toward the smooth muscle cells. Following SKCa activation, smooth muscle hyperpolarization is preferentially evoked by electrical coupling through myoendothelial gap junctions, whereas, following IKCa activation, K+ efflux can activate smooth muscle Kir2.1 and/or Na+/K+-ATPase. EDHF-mediated responses are altered by aging and various pathologies. Therapeutic interventions can restore these responses, suggesting that the improvement in the EDHF pathway contributes to their beneficial effect. A better characterization of EDHF-mediated responses should allow the determination of whether or not new drugable targets can be identified for the treatment of cardiovascular diseases.
41
Subramani, Jaganathan, Kandaswamy Kathirvel, Marie Dennis Marcus Leo, Guruprasad Kuntamallappanavar, Thakur Uttam Singh, and Santosh Kumar Mishra. "Atorvastatin Restores the Impaired Vascular Endothelium-dependent Relaxations Mediated by Nitric Oxide and Endothelium-derived Hyperpolarizing Factors but Not Hypotension in Sepsis." Journal of Cardiovascular Pharmacology 54, no. 6 (2009): 526–34. http://dx.doi.org/10.1097/fjc.0b013e3181bfafd6.
Full text
42
Horibe, Mayumi, Koji Ogawa, Ju-Tae Sohn, and Paul A. Murray. "Propofol Attenuates Acetylcholine-induced Pulmonary Vasorelaxation." Anesthesiology 93, no. 2 (2000): 447–55. http://dx.doi.org/10.1097/00000542-200008000-00024.
Full textAbstract:
Background The mechanism by which propofol selectively attenuates the pulmonary vasodilator response to acetylcholine is unknown. The goals of this study were to identify the contributions of endogenous endothelial mediators (nitric oxide [NO], prostacyclin, and endothelium-derived hyperpolarizing factors [EDHFs]) to acetylcholine-induced pulmonary vasorelaxation, and to delineate the extent to which propofol attenuates responses to these endothelium-derived relaxing factors. Methods Canine pulmonary arterial rings were suspended for isometric tension recording. The effects of propofol on the vasorelaxation responses to acetylcholine, bradykinin, and the guanylyl cyclase activator, SIN-1, were assessed in phenylephrine-precontracted rings. The contributions of NO, prostacyclin, and EDHFs to acetylcholine-induced vasorelaxation were assessed in control and propofol-treated rings by pretreating the rings with a NO synthase inhibitor (l-NAME), a cyclooxygenase inhibitor (indomethacin), and a cytochrome P450 inhibitor (clotrimazole or SKF 525A) alone and in combination. Results Propofol caused a dose-dependent rightward shift in the acetylcholine dose-response relation, whereas it had no effect on the pulmonary vasorelaxant responses to bradykinin or SIN-1. Cyclooxygenase inhibition only attenuated acetylcholine-induced relaxation at high concentrations of the agonist. NO synthase inhibition and cytochrome P450 inhibition each attenuated the response to acetylcholine, and combined inhibition abolished the response. Propofol further attenuated acetylcholine-induced relaxation after NO synthase inhibition and after cytochrome P450 inhibition. Conclusion These results suggest that acetylcholine-induced pulmonary vasorelaxation is mediated by two components: NO and a cytochrome P450 metabolite likely to be an EDHF. Propofol selectively attenuates acetylcholine-induced relaxation by inhibiting both of these endothelium-derived mediators.
43
Campbell, William B., and David R. Harder. "Endothelium-Derived Hyperpolarizing Factors and Vascular Cytochrome P450 Metabolites of Arachidonic Acid in the Regulation of Tone." Circulation Research 84, no. 4 (1999): 484–88. http://dx.doi.org/10.1161/01.res.84.4.484.
Full text
44
Mentek, Marielle, Marie Baldazza, Jessica Morand, et al. "0169 : Effects of intermittent hypoxia on rat ophthalmic artery reactivity: role of endothelin 1, oxidative stress and endothelium derived hyperpolarizing factors." Archives of Cardiovascular Diseases Supplements 8, no. 3 (2016): 216. http://dx.doi.org/10.1016/s1878-6480(16)30397-4.
Full text
45
Moreno, Juan Manuel, Rosemary Wangensteen, Juan Sainz, et al. "Role of endothelium-derived relaxing factors in the renal response to vasoactive agents in hypothyroid rats." American Journal of Physiology-Endocrinology and Metabolism 285, no. 1 (2003): E182—E188. http://dx.doi.org/10.1152/ajpendo.00558.2002.
Full textAbstract:
This study analyzed the role of nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) in the abnormal renal vascular reactivity of hypothyroid rats. Renal responses to vasoconstrictors [VC: phenylephrine (PHE) and ANG II] and vasodilators [VD: ACh, sodium nitroprusside (SNP), and papaverine (PV)] were studied in kidneys from control and hypothyroid rats under normal conditions and after NO or EDHF blockade. NO was blocked by the administration of Nω-nitro-l-arginine methyl ester (l-NAME) and EDHF by the administration of tetraethylammonium (TEA) or by an increased extracellular K+. The response to VC was also evaluated after endothelium removal. Hypothyroid kidneys showed reduced responsiveness to PHE and a normal response to ANG II. l-NAME and TEA administration produced an increased sensitivity to PHE and to ANG II in control preparations. l-NAME also increased the response to PHE in hypothyroid kidneys, but the differences between control and hypothyroid kidneys were maintained. TEA administration did not change the response to either VC in hypothyroid preparations. In endothelium-removed preparations, TEA was unable to increase pressor responsiveness to VC. Hypothyroid kidneys showed reduced responsiveness to ACh and SNP and normal response to PV. The differences between hypothyroid and control preparations in the responses to ACh and SNP were maintained after l-NAME or increased K+. In conclusion, this study shows that 1) the attenuated response to PHE in hypothyroidism is not related to an increased production of endothelium-derived relaxing factors NO and EDHF; 2) the response to VC in hypothyroid preparations is insensitive to EDHF blockade; and 3) hypothyroid preparations have a reduced reactivity to the NO donor, and NO-independent vasodilatation remains unaffected.
46
Fitzgerald, Sharyn M., Homaira Bashari, Jessica A. Cox, Helena C. Parkington, and Roger G. Evans. "Contributions of endothelium-derived relaxing factors to control of hindlimb blood flow in the mouse in vivo." American Journal of Physiology-Heart and Circulatory Physiology 293, no. 2 (2007): H1072—H1082. http://dx.doi.org/10.1152/ajpheart.00072.2007.
Full textAbstract:
We determined the contributions of various endothelium-derived relaxing factors to control of basal vascular tone and endothelium-dependent vasodilation in the mouse hindlimb in vivo. Under anesthesia, catheters were placed in a carotid artery, jugular vein, and femoral artery (for local hindlimb circulation injections). Hindlimb blood flow (HBF) was measured by transit-time ultrasound flowmetry. Nω-nitro-l-arginine methyl ester (l-NAME, 50 mg/kg plus 10 mg·kg−1·h−1), to block nitric oxide (NO) production, altered basal hemodynamics, increasing mean arterial pressure (30 ± 3%) and reducing HBF (−30 ± 12%). Basal hemodynamics were not significantly altered by indomethacin (10 mg·kg−1·h−1), charybdotoxin (ChTx, 3 × 10−8 mol/l), apamin (2.5 × 10−7 mol/l), or ChTx plus apamin (to block endothelium-derived hyperpolarizing factor; EDHF). Hyperemic responses to local injection of acetylcholine (2.4 μg/kg) were reproducible in vehicle-treated mice and were not significantly attenuated by l-NAME alone, indomethacin alone, l-NAME plus indomethacin with or without co-infusion of diethlyamine NONOate to restore resting NO levels, ChTx alone, or apamin alone. Hyperemic responses evoked by acetylcholine were reduced by 29 ± 11% after combined treatment with apamin plus charybdotoxin, and the remainder was virtually abolished by additional treatment with l-NAME but not indomethacin. None of the treatments altered the hyperemic response to sodium nitroprusside (5 μg/kg). We conclude that endothelium-dependent vasodilation in the mouse hindlimb in vivo is mediated by both NO and EDHF. EDHF can fully compensate for the loss of NO, but this cannot be explained by tonic inhibition of EDHF by NO. Control of basal vasodilator tone in the mouse hindlimb is dominated by NO.
47
Fuloria, Mamta, Thuy K. Smith, and Judy L. Aschner. "Role of 5,6-epoxyeicosatrienoic acid in the regulation of newborn piglet pulmonary vascular tone." American Journal of Physiology-Lung Cellular and Molecular Physiology 283, no. 2 (2002): L383—L389. http://dx.doi.org/10.1152/ajplung.00444.2001.
Full textAbstract:
We examined the responses of newborn piglet pulmonary resistance arteries (PRAs) to 5,6-epoxyeicosatrienoic acid (5,6-EET), a cytochrome P-450 metabolite of arachidonic acid. In PRAs preconstricted with a thromboxane A2 mimetic, 5,6-EET caused a concentration-dependent dilation. This dilation was partially inhibited by the combination of charybdotoxin (CTX) and apamin, inhibitors of large and small conductance calcium-dependent potassium (KCa) channels, and was abolished by depolarization of vascular smooth muscle with KCl. Disruption of the endothelium significantly attenuated the dilation, suggesting involvement of one or more endothelium-derived vasodilator pathways in this response. The dilation was partially inhibited by nitro-l-arginine (l-NA), an inhibitor of nitric oxide synthase (NOS), but was unaffected by indomethacin, a cyclooxygenase (COX) inhibitor. The combined inhibition of NOS and KCa channels with l-NA, CTX, and apamin abolished 5,6-EET-mediated dilation. Similarly, combined inhibition of NOS and COX abolished the response. We conclude that 5,6-EET is a potent vasodilator in newborn piglet PRAs. This dilation is mediated by redundant pathways that include release of nitric oxide (NO) and COX metabolites and activation of KCa channels. The endothelium dependence of this response suggests that 5,6-EET is not itself an endothelium-derived hyperpolarizing factor (EDHF) but may induce the release of one or more endothelium-derived relaxing factors, such as NO and/or EDHF.
48
Matsumoto, Takayuki, Eri Noguchi, Keiko Ishida, Tsuneo Kobayashi, Nobuhiro Yamada, and Katsuo Kamata. "Metformin normalizes endothelial function by suppressing vasoconstrictor prostanoids in mesenteric arteries from OLETF rats, a model of type 2 diabetes." American Journal of Physiology-Heart and Circulatory Physiology 295, no. 3 (2008): H1165—H1176. http://dx.doi.org/10.1152/ajpheart.00486.2008.
Full textAbstract:
We previously reported that in mesenteric arteries from aged Otsuka Long-Evans Tokushima fatty (OLETF) rats (a type 2 diabetes model) endothelium-derived hyperpolarizing factor (EDHF)-type relaxation is impaired while endothelium-derived contracting factor (EDCF)-mediated contraction is enhanced (Matsumoto T, Kakami M, Noguchi E, Kobayashi T, Kamata K. Am J Physiol Heart Circ Physiol 293: H1480–H1490, 2007). Here we investigated whether acute and/or chronic treatment with metformin might improve this imbalance between the effects of the above endothelium-derived factors in mesenteric arteries isolated from OLETF rats. In acute studies on OLETF mesenteric arteries, ACh-induced relaxation was impaired and the relaxation became weaker at high ACh concentrations. Both metformin and 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside [AICAR, an AMP-activated protein kinase (AMPK) activator that is also activated by metformin] 1) diminished the tendency for the relaxation to reverse at high ACh concentrations and 2) suppressed both ACh-induced EDCF-mediated contraction and ACh-stimulated production of prostanoids (thromboxane A2 and PGE2). In studies on OLETF arteries from chronically treated animals, metformin treatment (300 mg·kg−1·day−1 for 4 wk) 1) improved ACh-induced nitric oxide- or EDHF-mediated relaxation and cyclooxygenase (COX)-mediated contraction, 2) reduced EDCF-mediated contraction, 3) suppressed production of prostanoids, and 4) reduced superoxide generation. Metformin did not alter the protein expressions of endothelial nitric oxide synthase (eNOS), phospho-eNOS (Ser1177), or COX-1, but it increased COX-2 protein. These results suggest that metformin improves endothelial functions in OLETF mesenteric arteries by suppressing vasoconstrictor prostanoids and by reducing oxidative stress. Our data suggest that within the timescale studied here, metformin improves endothelial function through this direct mechanism, rather than by improving metabolic abnormalities.
49
Imig, John D. "Eicosanoid blood vessel regulation in physiological and pathological states." Clinical Science 134, no. 20 (2020): 2707–27. http://dx.doi.org/10.1042/cs20191209.
Full textAbstract:
Abstract Arachidonic acid can be metabolized in blood vessels by three primary enzymatic pathways; cyclooxygenase (COX), lipoxygenase (LO), and cytochrome P450 (CYP). These eicosanoid metabolites can influence endothelial and vascular smooth muscle cell function. COX metabolites can cause endothelium-dependent dilation or constriction. Prostaglandin I2 (PGI2) and thromboxane (TXA2) act on their respective receptors exerting opposing actions with regard to vascular tone and platelet aggregation. LO metabolites also influence vascular tone. The 12-LO metabolite 12S-hydroxyeicosatrienoic acid (12S-HETE) is a vasoconstrictor whereas the 15-LO metabolite 11,12,15-trihydroxyeicosatrienoic acid (11,12,15-THETA) is an endothelial-dependent hyperpolarizing factor (EDHF). CYP enzymes produce two types of eicosanoid products: EDHF vasodilator epoxyeicosatrienoic acids (EETs) and the vasoconstrictor 20-HETE. The less-studied cross-metabolites generated from arachidonic acid metabolism by multiple pathways can also impact vascular function. Likewise, COX, LO, and CYP vascular eicosanoids interact with paracrine and hormonal factors such as the renin–angiotensin system and endothelin-1 (ET-1) to maintain vascular homeostasis. Imbalances in endothelial and vascular smooth muscle cell COX, LO, and CYP metabolites in metabolic and cardiovascular diseases result in vascular dysfunction. Restoring the vascular balance of eicosanoids by genetic or pharmacological means can improve vascular function in metabolic and cardiovascular diseases. Nevertheless, future research is necessary to achieve a more complete understanding of how COX, LO, CYP, and cross-metabolites regulate vascular function in physiological and pathological states.
50
Sorop, Oana, Mieke van den Heuvel, Nienke S. van Ditzhuijzen, et al. "Coronary microvascular dysfunction after long-term diabetes and hypercholesterolemia." American Journal of Physiology-Heart and Circulatory Physiology 311, no. 6 (2016): H1339—H1351. http://dx.doi.org/10.1152/ajpheart.00458.2015.
Full textAbstract:
Coronary microvascular dysfunction (CMD) has been proposed as an important component of diabetes mellitus (DM)- and hypercholesterolemia-associated coronary artery disease (CAD). Previously we observed that 2.5 mo of DM and high-fat diet (HFD) in swine blunted bradykinin (BK)-induced vasodilation and attenuated endothelin (ET)-1-mediated vasoconstriction. Here we studied the progression of CMD after 15 mo in the same animal model of CAD. Ten male swine were fed a HFD in the absence (HFD, n = 5) or presence of streptozotocin-induced DM (DM + HFD, n = 5). Responses of small (∼300-μm-diameter) coronary arteries to BK, ET-1, and the nitric oxide (NO) donor S-nitroso- N-acetylpenicillamine were examined in vitro and compared with those of healthy (Normal) swine ( n = 12). Blood glucose was elevated in DM + HFD (17.6 ± 4.5 mmol/l) compared with HFD (5.1 ± 0.4 mmol/l) and Normal (5.8 ± 0.6 mmol/l) swine, while cholesterol was markedly elevated in DM + HFD (16.8 ± 1.7 mmol/l) and HFD (18.1 ± 2.6 mmol/l) compared with Normal (2.1 ± 0.2 mmol/l) swine (all P < 0.05). Small coronary arteries showed early atherosclerotic plaques in HFD and DM + HFD swine. Surprisingly, DM + HFD and HFD swine maintained BK responsiveness compared with Normal swine due to an increase in NO availability relative to endothelium-derived hyperpolarizing factors. However, ET-1 responsiveness was greater in HFD and DM + HFD than Normal swine (both P < 0.05), resulting mainly from ETB receptor-mediated vasoconstriction. Moreover, the calculated vascular stiffness coefficient was higher in DM + HFD and HFD than Normal swine (both P < 0.05). In conclusion, 15 mo of DM + HFD, as well as HFD alone, resulted in CMD. Although the overall vasodilation to BK was unperturbed, the relative contributions of NO and endothelium-derived hyperpolarizing factor pathways were altered. Moreover, the vasoconstrictor response to ET-1 was enhanced, involving the ETB receptors. In conjunction with our previous study, these findings highlight the time dependence of the phenotype of CMD.