Journal articles: 'Dahl salt sensitive rat'

1

Liu, Yong, Ravinder J. Singh, Kristie Usa, Brian C. Netzel, and Mingyu Liang. "Renal medullary 11β-hydroxysteroid dehydrogenase type 1 in Dahl salt-sensitive hypertension." Physiological Genomics 36, no. 1 (December 2008): 52–58. http://dx.doi.org/10.1152/physiolgenomics.90283.2008.

Full text

Abstract:

The Dahl salt-sensitive rat is a widely used model of human salt-sensitive forms of hypertension. The kidney plays an important role in the pathogenesis of Dahl salt-sensitive hypertension, but the molecular mechanisms involved remain a subject of intensive investigation. Gene expression profiling studies suggested that 11β-hydroxysteroid dehydrogenase type 1 might be dysregulated in the renal medulla of Dahl salt-sensitive rats. Additional analysis confirmed that renal medullary expression of 11β-hydroxysteroid dehydrogenase type 1 was downregulated by a high-salt diet in SS-13BN rats, a consomic rat strain with reduced blood pressure salt sensitivity, but not in Dahl salt-sensitive rats. 11β-Hydroxysteroid dehydrogenase type 1 is known to convert inactive 11-dehydrocorticosterone to active corticosterone. The urinary corticosterone/11-dehydrocorticosterone ratio as well as urinary excretion of corticosterone was higher in Dahl salt-sensitive rats than in SS-13BN rats. Knockdown of renal medullary 11β-hydroxysteroid dehydrogenase type 1 with small-interfering RNA attenuated the early phase of salt-induced hypertension in Dahl salt-sensitive rats and reduced urinary excretion of corticosterone. Knockdown of 11β-hydroxysteroid dehydrogenase type 1 did not affect blood pressure in SS-13BN rats. Long-term attenuation of salt-induced hypertension was achieved with small hairpin RNA targeting renal medullary 11β-hydroxysteroid dehydrogenase type 1. In summary, we have demonstrated that suppression of 11β-hydroxysteroid dehydrogenase type 1 expression in the renal medulla attenuates salt-induced hypertension in Dahl salt-sensitive rats.

APA, Harvard, Vancouver, ISO, and other styles

2

Hong, Nancy J., Agustin Gonzalez-Vicente, Fara Saez, and Jeffrey L. Garvin. "Mechanisms of decreased tubular flow-induced nitric oxide in Dahl salt-sensitive rat thick ascending limbs." American Journal of Physiology-Renal Physiology 321, no. 3 (September 1, 2021): F369—F377. http://dx.doi.org/10.1152/ajprenal.00124.2021.

Full text

Abstract:

The Dahl rat has been used extensively to study the causes and effects of salt-sensitive hypertension. Our study suggests that more complex processes other than simple scavenging of nitric oxide (NO) by superoxide lead to less NO production in thick ascending limbs of the Dahl salt-sensitive rat. The predominant mechanism involved depends on dietary salt. Impaired flow-induced NO production in thick ascending limbs most likely contributes to the Na+ retention associated with salt-sensitive hypertension.

APA, Harvard, Vancouver, ISO, and other styles

3

Gillis, Ellen E., Jan M. Williams, Michael R. Garrett, Jennifer N. Mooney, and Jennifer M. Sasser. "The Dahl salt-sensitive rat is a spontaneous model of superimposed preeclampsia." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 309, no. 1 (July 1, 2015): R62—R70. http://dx.doi.org/10.1152/ajpregu.00377.2014.

Full text

Abstract:

The mechanisms of the pathogenesis of preeclampsia, a leading cause of maternal morbidity and death worldwide, are poorly understood in part due to a lack of spontaneous animal models of the disease. We hypothesized that the Dahl salt-sensitive (S) rat, a genetic model of hypertension and kidney disease, is a spontaneous model of superimposed preeclampsia. The Dahl S was compared with the Sprague-Dawley (SD) rat, a strain with a well-characterized normal pregnancy, and the spontaneously hypertensive rat (SHR), a genetic model of hypertension that does not experience a preeclamptic phenotype despite preexisting hypertension. Mean arterial pressure (MAP, measured via telemetry) was elevated in the Dahl S and SHR before pregnancy, but hypertension was exacerbated during pregnancy only in Dahl S. In contrast, SD and SHR exhibited significant reductions in MAP consistent with normal pregnancy. Dahl S rats exhibited a severe increase in urinary protein excretion, glomerulomegaly, increased placental hypoxia, increased plasma soluble fms-like tyrosine kinase-1 (sFlt-1), and increased placental production of tumor necrosis factor-α (TNF-α). The Dahl S did not exhibit the expected decrease in uterine artery resistance during late pregnancy in contrast to the SD and SHR. Dahl S pups and litter sizes were smaller than in the SD. The Dahl S phenotype is consistent with many of the characteristics observed in human superimposed preeclampsia, and we propose that the Dahl S should be considered further as a spontaneous model to improve our understanding of the pathogenesis of superimposed preeclampsia and to identify and test new therapeutic targets for its treatment.

APA, Harvard, Vancouver, ISO, and other styles

4

Tran, Kenneth, June-Chiew Han, Andrew J. Taberner, Carolyn J. Barrett, Edmund J. Crampin, and Denis S. Loiselle. "Myocardial energetics is not compromised during compensated hypertrophy in the Dahl salt-sensitive rat model of hypertension." American Journal of Physiology-Heart and Circulatory Physiology 311, no. 3 (September 1, 2016): H563—H571. http://dx.doi.org/10.1152/ajpheart.00396.2016.

Full text

Abstract:

Salt-induced hypertension leads to development of left ventricular hypertrophy in the Dahl salt-sensitive (Dahl/SS) rat. Before progression to left ventricular failure, the heart initially undergoes a compensated hypertrophic response. We hypothesized that changes in myocardial energetics may be an early indicator of transition to failure. Dahl/SS rats and their salt-resistant consomic controls (SS-13BN) were placed on either a low- or high-salt diet to generate four cohorts: Dahl-SS rats on a low- (Dahl-LS) or high-salt diet (Dahl-HS), and SS-13BN rats on a low- (SSBN-LS) or high-salt diet (SSBN-HS). We isolated left ventricular trabeculae and characterized their mechanoenergetic performance. Our results show, at most, modest effects of salt-induced compensated hypertrophy on myocardial energetics. We found that the Dahl-HS cohort had a higher work-loop heat of activation (estimated from the intercept of the heat vs. relative afterload relationship generated from work-loop contractions) relative to the SSBN-HS cohort and a higher economy of contraction (inverse of the slope of the heat vs. active stress relation) relative to the Dahl-LS cohort. The maximum extent of shortening and maximum shortening velocity of the Dahl/SS groups were higher than those of the SS-13BN groups. Despite these differences, no significant effect of salt-induced hypertension was observed for either peak work output or peak mechanical efficiency during compensated hypertrophy.

APA, Harvard, Vancouver, ISO, and other styles

5

Kushiro, Toshio, Hirotaka Fujita, Ryohei Hisaki, Takae Asai, Izumi Ichiyama, Yasuyuki Kitahara, Miyuki Koike, et al. "Oxidative Stress in the Dahl Salt-Sensitive Hypertensive Rat." Clinical and Experimental Hypertension 27, no. 1 (January 2005): 9–15. http://dx.doi.org/10.1081/ceh-200044244.

Full text

APA, Harvard, Vancouver, ISO, and other styles

6

Husted, R. F., T. Takahashi, and J. B. Stokes. "IMCD cells cultured from Dahl S rats absorb more Na+ than Dahl R rats." American Journal of Physiology-Renal Physiology 271, no. 5 (November 1, 1996): F1029—F1036. http://dx.doi.org/10.1152/ajprenal.1996.271.5.f1029.

Full text

Abstract:

Dahl salt-sensitive (S) rats develop hypertension in response to a high-salt diet, whereas Dahl salt-resistant (R) rats do not. There is good evidence that the Dahl S kidneys have diminished natriuretic capacity. We studied the rate of Na+ transport by primary cultures of the inner medullary collecting duct from these two strains to determine whether there were intrinsic differences. Monolayers obtained from prehypertensive S rats transported Na+ at twice the rate as monolayers from age-matched R rats. Mineralocorticoid and glucocorticoid hormones increased Na+ transport from both strains; the S rat monolayers always displayed higher transport rates than R rat monolayers with the same treatment. The Na+ entry pathway in both S and R rat monolayers was via an Na+ channel. The difference in Na+ transport was not explained by a difference in the metabolism of corticosterone, ATP content, citrate synthase activity, ultrastructural appearance, or rate of maturation. Monolayers from S rats tended to have higher protein and DNA content, but these differences could not account for the difference in Na+ transport. Anion secretion in response to adenosine 3',5'-cyclic monophosphate agonists was similar. These results demonstrate intrinsic differences in renal tubular cells that may play an important role in the pathogenesis of salt-sensitive hypertension.

APA, Harvard, Vancouver, ISO, and other styles

7

Hirawa, N., Y. Uehara, Y. Kawabata, A. Numabe, S. Takada, H. Nagoshi, T. Gomi, T. Ikeda, and M. Omata. "Hachimi-jio-gan Extract Protects the Kidney from Hypertensive Injury in Dahl Salt-sensitive Rat." American Journal of Chinese Medicine 24, no. 03n04 (January 1996): 241–54. http://dx.doi.org/10.1142/s0192415x9600030x.

Full text

Abstract:

We investigated whether the Chinese herbal remedy, Hachimi-jio-gan extract, attenuates the renal injury seen in salt-induced hypertension in Dahl salt-sensitive (Dahl S) rats. Administration of this extract for 5 weeks dose-dependently decreased systolic blood pressure in Dahl S rats fed with a high-salt (2% NaCI) diet. This blood pressure reduction was associated with a decrease in cardiac mass and in thickness of the aortic wall. Urinary excretion of prostaglandin E2 was increased and glomerular filtration rate was improved with this treatment. Glomerulosclerosis and arterial injury in the kidney were morphologically improved. These data suggest that Hachimi-jio-gan extract exhibits an antihypertensive effect, which is associated with partial resolution of renal injury in salt-induced hypertension.

APA, Harvard, Vancouver, ISO, and other styles

8

Bugenhagen, Scott M., Allen W. Cowley, and Daniel A. Beard. "Identifying physiological origins of baroreflex dysfunction in salt-sensitive hypertension in the Dahl SS rat." Physiological Genomics 42, no. 1 (June 2010): 23–41. http://dx.doi.org/10.1152/physiolgenomics.00027.2010.

Full text

Abstract:

Salt-sensitive hypertension is known to be associated with dysfunction of the baroreflex control system in the Dahl salt-sensitive (SS) rat. However, neither the physiological mechanisms nor the genomic regions underlying the baroreflex dysfunction seen in this rat model are definitively known. Here, we have adopted a mathematical modeling approach to investigate the physiological and genetic origins of baroreflex dysfunction in the Dahl SS rat. We have developed a computational model of the overall baroreflex heart rate control system based on known physiological mechanisms to analyze telemetry-based blood pressure and heart rate data from two genetic strains of rat, the SS and consomic SS.13BN, on low- and high-salt diets. With this approach, physiological parameters are estimated, unmeasured physiological variables related to the baroreflex control system are predicted, and differences in these quantities between the two strains of rat on low- and high-salt diets are detected. Specific findings include: a significant selective impairment in sympathetic gain with high-salt diet in SS rats and a protection from this impairment in SS.13BN rats, elevated sympathetic and parasympathetic offsets with high-salt diet in both strains, and an elevated sympathetic tone with high-salt diet in SS but not SS.13BN rats. In conclusion, we have associated several important physiological parameters of the baroreflex control system with chromosome 13 and have begun to identify possible physiological mechanisms underlying baroreflex impairment and hypertension in the Dahl SS rat that may be further explored in future experimental and modeling-based investigation.

APA, Harvard, Vancouver, ISO, and other styles

9

Huang, Pan, Yaqian Huang, Boyang Lv, Heng Zhang, Jia Liu, Guosheng Yang, Yinghong Tao, et al. "Endogenous Taurine Downregulation Is Required for Renal Injury in Salt-Sensitive Hypertensive Rats via CBS/H2S Inhibition." Oxidative Medicine and Cellular Longevity 2021 (August 25, 2021): 1–20. http://dx.doi.org/10.1155/2021/5530907.

Full text

Abstract:

Although taurine is known to exert an antihypertensive effect, it is unclear whether it is involved in the mechanism for hypertension-related target organ injury. To reveal the role of endogenous taurine in renal injury formation during salt-sensitive hypertension and clarify its mechanisms, both salt-sensitive Dahl rats and salt-resistant SS-13BN rats were fed a high-salt diet (8% NaCl) and given 2% taurine for 6 weeks. Rat systolic blood pressure (SBP) was measured by the tail-cuff method and artery catheterization. Kidney ultrastructure was observed under an electron microscope. Taurine content and mRNA and protein levels of taurine synthases, cysteine dioxygenase type 1 (CDO1) and cysteine sulfinic acid decarboxylase (CSAD), were decreased in Dahl rats fed a high-salt diet. However, taurine supplementation and the resulting increase in renal taurine content reduced the increased SBP and improved renal function and structural damage in high-salt diet-fed Dahl rats. In contrast, taurine did not affect SS-13BN SBP and renal function and structure. Taurine intervention increased the renal H2S content and enhanced cystathionine-β-synthase (CBS) expression and activity in Dahl rats fed a high-salt diet. Taurine reduced the renin, angiotensin II, and aldosterone contents and the levels of oxidative stress indices in Dahl rat renal tissues but increased antioxidant capacity, antioxidant enzyme activity, and protein expression. However, taurine failed to achieve this effect in the renal tissue of SS-13BN rats fed a high-salt diet. Pretreatment with the CBS inhibitor HA or renal CBS knockdown inhibited H2S generation and subsequently blocked the effect of taurine on renin, superoxide dismutase 1 (SOD1), and superoxide dismutase 2 (SOD2) levels in high-salt-stimulated Dahl renal slices. In conclusion, the downregulation of endogenous taurine production resulted in a decrease in the renal CBS/H2S pathway. This decrease subsequently promoted renin-angiotensin-aldosterone system (RAAS) activation and oxidative stress in the kidney, ultimately contributing to renal injury in salt-sensitive Dahl rats.

APA, Harvard, Vancouver, ISO, and other styles

10

Boegehold, M. A., L. J. Huffman, and G. A. Hedge. "Peripheral vascular resistance and regional blood flows in hypertensive Dahl rats." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 261, no. 4 (October 1, 1991): R934—R938. http://dx.doi.org/10.1152/ajpregu.1991.261.4.r934.

Full text

Abstract:

The aim of this study was to determine whether different organs undergo similar increases in vascular resistance with hypertension in the Dahl salt-sensitive rat. Cardiac output and organ blood flows were measured with microspheres in anesthetized salt-sensitive and salt-resistant rats fed a high- (7%) or normal- (0.45%) salt diet for 4 wk. High salt intake produced hypertension only in salt-sensitive rats. Cardiac index for the hypertensive group was not different from that for any other group, whereas peripheral resistance index was elevated in proportion to arterial pressure. There were no differences among groups in the fraction of cardiac output supplying the myocardium, intestine, diaphragm, spinotrapezius muscle, or gracilis muscle. The fraction of cardiac output supplying the kidneys was lower in salt-sensitive rats (13%) than in salt-resistant rats (17%) and, among salt-sensitive rats, lowest in the high-salt group. Therefore all the organs studied contribute to increased total peripheral resistance in the hypertensive Dahl rat, with the renal vasculature undergoing the largest resistance increase. Different muscles undergo similar increases in vascular resistance, despite differences in the microvascular abnormalities accompanying salt-induced hypertension.

APA, Harvard, Vancouver, ISO, and other styles

11

Cowley, Allen W., Chun Yang, Vikash Kumar, Jozef Lazar, Howard Jacob, Aron M. Geurts, Pengyuan Liu, Alex Dayton, Theresa Kurth, and Mingyu Liang. "Pappa2 is linked to salt-sensitive hypertension in Dahl S rats." Physiological Genomics 48, no. 1 (January 2016): 62–72. http://dx.doi.org/10.1152/physiolgenomics.00097.2015.

Full text

Abstract:

A 1.37 Mbp region of chromosome 13 previously identified by exclusion mapping was consistently associated with a reduction of salt-induced hypertension in the Dahl salt-sensitive (SS) rat. This region contained five genes that were introgressed from the salt-insensitive Brown Norway (BN) rat. The goal of the present study was to further narrow that region to identify the gene(s) most likely to protect from salt-induced hypertension. The studies yielded a subcongenic SS rat strain containing a 0.71 Mbp insert from BN (26-P strain) in which salt-induced hypertension was reduced by 24 mmHg. The region contained two protein-coding genes ( Astn1 and Pappa2) and a microRNA ( miR-488). Pappa2 mRNA in the renal cortex of the protected 26-P was 6- to 10-fold greater than in SS fed a 0.4% NaCl diet but was reduced to levels observed in SS when fed 8.0% NaCl diet for 7 days. Compared with brain nuclei (NTS, RVLM, CVLM) and the adrenal gland, Pappa2 in the renal cortex was the only gene found to be differentially expressed between SS and 26-P and that responded to changes of salt diet. Immunohistochemistry studies found Pappa2 localized in the cytosol of the epithelial cells of the cortical thick ascending limbs. In more distal segments of the renal tubules, it was observed within tubular lumens and most notably bound to the apical membranes of the intercalated cells of collecting ducts. We conclude that we have identified a variant form of Pappa2 that can protect against salt-induced hypertension in the Dahl S rat.

APA, Harvard, Vancouver, ISO, and other styles

12

Liclican, Elvira L., John C. McGiff, John R. Falck, and Mairéad A. Carroll. "Failure to upregulate the adenosine2A receptor-epoxyeicosatrienoic acid pathway contributes to the development of hypertension in Dahl salt-sensitive rats." American Journal of Physiology-Renal Physiology 295, no. 6 (December 2008): F1696—F1704. http://dx.doi.org/10.1152/ajprenal.90502.2008.

Full text

Abstract:

Adenosine-activated renovascular dilatation in Sprague-Dawley (SD) rats is mediated by stimulating adenosine2A receptors (A2AR), which is linked to epoxyeicosatrienoic acid (EET) synthesis. The A2AR-EET pathway is upregulated by high salt (HS) intake in normotensive SD rats. Because this pathway is antipressor, we examined the role of the A2AR-EET pathway in Dahl salt-sensitive (SS) rats. Male Dahl salt-resistant (SR) and SS rats were fed either HS (8.0% NaCl) or normal salt (NS; 0.4% NaCl) diet for 7 days. On day 8, isolated kidneys were perfused with Krebs-Henseleit buffer containing indomethacin and NG-nitro-l-arginine methyl ester and preconstricted with phenylephrine. Bolus injections of the stable adenosine analog 2-chloroadenosine (2-CA; 0.1–20 μg) elicited dose-dependent dilation in both Dahl SR and SS rats. Dahl SR rats fed a HS diet demonstrated a greater renal vasodilator response to 10 μg of 2-CA, as measured by the reduction in renal perfusion pressure, than that of Dahl SR rats fed a NS diet (−104 ± 6 vs. −77 ± 7 mmHg, respectively; P < 0.05). In contrast, Dahl SS rats did not exhibit a difference in the vasodilator response to 2-CA whether fed NS or HS diet (96 ± 6 vs. 104 ± 13 mmHg in NS- and HS-fed rats, respectively). In Dahl SR but not Dahl SS rats, HS intake significantly increased purine flux, augmented the protein expression of A2AR and the cytochrome P-450 2C23 and 2C11 epoxygenases, and elevated the renal efflux of EETs. Thus the Dahl SR rat is able to respond to HS intake by recruiting EET formation, whereas the Dahl SS rat appears to have exhausted its ability to increase EET synthesis above the levels observed on NS intake, and this inability of Dahl SS rats to upregulate the A2AR-EET pathway in response to salt loading may contribute to the development of salt-sensitive hypertension.

APA, Harvard, Vancouver, ISO, and other styles

13

Speed, Joshua S., Babbette LaMarca, Hunter Berry, Kathy Cockrell, Eric M. George, and Joey P. Granger. "Renal medullary endothelin-1 is decreased in Dahl salt-sensitive rats." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 301, no. 2 (August 2011): R519—R523. http://dx.doi.org/10.1152/ajpregu.00207.2011.

Full text

Abstract:

Although it is well established that the renal endothelin (ET-1) system plays an important role in regulating sodium excretion and blood pressure through activation of renal medullary ETB receptors, the role of this system in Dahl salt-sensitive (DS) hypertension is unclear. The purpose of this study was to determine whether the DS rat has abnormalities in the renal medullary endothelin system when maintained on a high sodium intake. The data indicate that Dahl salt-resistant rats (DR) on a high-salt diet had a six-fold higher urinary endothelin excretion than in the DR rats with low Na+ intake (17.8 ± 4 pg/day vs. 112 ± 44 pg/day). In sharp contrast, urinary endothelin levels increased only twofold in DS rats in response to a high Na+ intake (13 ± 2 pg/day vs. 29.8 ± 5.5 pg/day). Medullary endothelin concentration in DS rats on a high-Na+ diet was also significantly lower than DR rats on a high-Na+ diet (31 ± 2.8 pg/mg vs. 70.9 ± 5 pg/mg). Furthermore, DS rats had a significant reduction in medullary ETB receptor expression compared with DR rats while on a high-Na+ diet. Finally, chronic infusion of ET-1 directly into the renal medulla blunted Dahl salt-sensitive hypertension. These data indicate that a decrease in medullary production of ET-1 in the DS rat could play an important role in the development of salt-sensitive hypertension observed in the DS rat.

APA, Harvard, Vancouver, ISO, and other styles

14

Rapp, J. P. "Genetic analysis of hypertension in the Dahl salt-sensitive rat." Journal of Experimental Animal Science 41, no. 1-2 (March 2000): 5–6. http://dx.doi.org/10.1016/s0939-8600(00)80017-6.

Full text

APA, Harvard, Vancouver, ISO, and other styles

15

Sunga, Paul S., and Simon W. Rabkin. "Angiotensin II induced alteration of cyclic adenosine 3′,5′-monophosphate generation in the hypertrophic myocardium of Dahl salt-sensitive rat on a high-salt diet." Canadian Journal of Physiology and Pharmacology 72, no. 6 (June 1, 1994): 602–12. http://dx.doi.org/10.1139/y94-086.

Full text

Abstract:

The objective of this study was to explore the action of angiotensin II (AII) on cardiac contractility and cyclic AMP (cAMP) generation by forskolin and isoproterenol in the hypertrophic myocardium of the salt-sensitive Dahl rat. Inbred Dahl S and Dahl R rats that had been on a diet supplemented with 6% NaCl were studied. The functional effects of the interaction of AII and forskolin on cardiac contractility were assessed in the isolated heart preparation. The effect on the cAMP signal transduction pathway was assessed in cardiomyocytes isolated from hearts of Dahl S and R rats. Dahl S rats developed cardiac hypertrophy on a high-salt diet, whereas Dahl R rats did not. Forskolin increased cardiac contractility, which was differently affected by AII, depending on whether the heart was from hypertrophied Dahl S rat or from the control Dahl R rat. All accentuated forskolin-induced increases in cardiac contractility in hypertrophic hearts but diminished forskolin-induced increases in contractility in the nonhypertrophied hearts. This response was reflected in the cAMP response to forskolin, in that AII decreased forskolin-induced increases in cAMP in the nonhypertrophic heart. AII had the reverse effect in cardiomyocytes from hypertrophied hearts, as AII increased forskolin-induced cAMP production. This was shown to be due to an AII receptor mediated effect, as it was antagonized by the AII receptor antagonist saralasin. The same effects of AII were found on isoproterenol-induced increases in cAMP. Similar results occurred in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX), suggesting that the effect was on cAMP production rather than cAMP degradation. This was attributed to an inhibitory G protein (Gi) mechanism, as the muscarinic agonist carbachol, which acts through Gi, produced the same effects as AII Furthermore, the effects of AII were abolished by pertussis toxin, which inactivates Gi. These data indicate a reversal of control by AII in the hypertrophic Dahl S heart in response to forskolin, which activates adenylyl cyclase directly on the catalytic subunit, converting the substrate, ATP, to cAMP, independent of the guanine nucleotide activated protein, and in response to isoproterenol, which activates adenylyl cyclase through G protein mechanisms. AII accentuated the forskolin-induced increase in cardiac contractility and cAMP generation in the hypertrophied ventricle but decreased both contractility and cAMP generation in nonhypertrophied hearts, suggesting that the process of cardiac hypertrophy in salt-sensitive Dahl rat may compensate for the reduction in intracellular cAMP by altering its regulatory control by AII.Key words: cardiac hypertrophy, angiotensin, forskolin, isoproterenol, adenylyl cyclase, Dahl rat.

APA, Harvard, Vancouver, ISO, and other styles

16

Tan, Dunyong Y., Shumei Meng, Garrick W. Cason, and R. Davis Manning. "Mechanisms of salt-sensitive hypertension: role of inducible nitric oxide synthase." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 279, no. 6 (December 1, 2000): R2297—R2303. http://dx.doi.org/10.1152/ajpregu.2000.279.6.r2297.

Full text

Abstract:

The goal of this study was to determine the role of inducible nitric oxide synthase (iNOS) in the arterial pressure, renal hemodynamic, renal excretory, and hormonal changes that occur in Dahl/Rapp salt-resistant (R) and salt-sensitive (S) rats during changes in Na intake. Thirty-two R and S rats, equipped with indwelling arterial and venous catheters, were subjected to low (0.87 mmol/day) or high (20.6 mmol/day) Na intake, and selective iNOS inhibition was achieved with intravenous aminoguanidine (AG, 12.3 mg · kg−1 · h−1). After 5 days of AG, mean arterial pressure increased to 121 ± 3% control in the R-high Na AG rats compared with 98 ± 1% control ( P < 0.05) in the R-high Na alone rats, and S-high Na rats increased their arterial pressure to 123 ± 3% control compared with 110 ± 2% control ( P < 0.05) in S-high Na alone rats. AG caused no significant changes in renal hemodynamics, urinary Na or H2O excretion, plasma renin activity, or cerebellar Ca-dependent NOS activity. The data suggest that nitric oxide produced by iNOS normally helps to prevent salt-sensitive hypertension in the Dahl R rat and decreases salt sensitivity in the Dahl S rat.

APA, Harvard, Vancouver, ISO, and other styles

17

Taylor, Erin B., Eric M. George, Michael J. Ryan, Michael R. Garrett, and Jennifer M. Sasser. "Immunological comparison of pregnant Dahl salt-sensitive and Sprague-Dawley rats commonly used to model characteristics of preeclampsia." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 321, no. 2 (August 1, 2021): R125—R138. http://dx.doi.org/10.1152/ajpregu.00298.2020.

Full text

Abstract:

The pregnant Dahl salt-sensitive (S) rat is an established preclinical model of superimposed spontaneous preeclampsia characterized by exacerbated hypertension, increased urinary protein excretion, and increased fetal demise. Because of the underlying immune system dysfunction present in preeclamptic pregnancies in humans, we hypothesized that the pregnant Dahl S rat would also have an altered immune status. Immune system activation was assessed during late pregnancy in the Dahl S model and compared with healthy pregnant Sprague-Dawley (SD) rats subjected to either a sham procedure or a procedure to reduce uterine perfusion pressure (RUPP). Circulating immunoglobulin and cytokine levels were measured by enzyme-linked immunosorbent assay (ELISA) and Milliplex bead assay, respectively, and percentages of circulating, splenic, and placental immune cells were determined using flow cytometry. The pregnant Dahl S rat exhibited an increase in CD4+ T cells, and specifically TNFα+CD4+ T cells, in the spleen compared with virgin Dahl S rats. The Dahl also had increased neutrophils and decreased B cells in the peripheral blood as compared with Dahl virgin rats. SD rats that received the RUPP procedure had increases in circulating monocytes and increased IFN-ɣ+CD4+ splenic T cells. Together these findings suggest that dysregulated T cell activity is an important factor in both the pregnant Dahl S rats and SD rats after the RUPP procedure.

APA, Harvard, Vancouver, ISO, and other styles

18

Cowen, L. A., M. R. Harold, C. M. Chen, R. E. Abbott, and D. Schachter. "Immunoglobulin and renal abnormalities in Dahl genetically hypertensive rat." American Journal of Physiology-Heart and Circulatory Physiology 261, no. 6 (December 1, 1991): H1895—H1902. http://dx.doi.org/10.1152/ajpheart.1991.261.6.h1895.

Full text

Abstract:

The Dahl salt-sensitive rat (DS) is a model of genetically determined arterial hypertension exacerbated by dietary salt. We report two additional abnormalities of DS rats, which are both genetically determined and enhanced by salt: 1) immunoglobulin disorders and 2) renal dysfunctions. These abnormalities precede and are not the result of the arterial hypertension. In young, prehypertensive DS rats the plasma and tissue concentrations of immunoglobulin (Ig) G, but not of IgM or IgA, are decreased compared with those of the salt-resistant strain (DR). A high-salt diet (8.0% NaCl) decreases the plasma and tissue IgG levels of DS but not of DR rats. Reduction of IgG in the DS strain results from both decreased synthesis and increased urinary excretion. Renal dysfunction in young, prehypertensive DS animals is manifested by increased excretion of high molecular weight proteins, including albumin, IgG, IgA, and IgM. The high-salt diet increases the urinary excretion of these proteins within 1-2 days, and the effect is much greater in DS compared with DR rats. The urinary excretion of IgG is selectively increased relative to immunoglobulin light chains, IgA and IgM in DS compared with DR animals. The present studies provide new markers characteristic of the DS phenotype and pose the issue of possible genetic or functional interrelationships among the salt-sensitive hypertension, immunoglobulin disorders, and renal dysfunctions.

APA, Harvard, Vancouver, ISO, and other styles

19

Mattson, David L., Melinda R. Dwinell, Andrew S. Greene, Anne E. Kwitek, Richard J. Roman, Howard J. Jacob, and Allen W. Cowley. "Chromosome substitution reveals the genetic basis of Dahl salt-sensitive hypertension and renal disease." American Journal of Physiology-Renal Physiology 295, no. 3 (September 2008): F837—F842. http://dx.doi.org/10.1152/ajprenal.90341.2008.

Full text

Abstract:

This study examined the genetic basis of hypertension and renal disease in Dahl SS/Mcwi (Dahl Salt-Sensitive) rats using a complete chromosome substitution panel of consomic rats in which each of the 20 autosomes and the X and Y chromosomes were individually transferred from the Brown Norway (BN) rat onto the Dahl SS/Mcwi genetic background. Male and female rats of each of the two parental and 22 consomic strains (10–12 rats/group) were fed a high-salt (8.0% NaCl) diet for 3 wk. Mean arterial blood pressure rose by 60 mmHg and urinary protein and albumin excretion increased 3- and 20-fold, respectively, in male SS/Mcwi rats compared with BN controls. Substitution of chromosomes 1, 5, 7, 8, 13, or 18 from the BN onto the SS/Mcwi background attenuated the development of hypertension, proteinuria, and albuminuria in male rats. In female rats, substitution of chromosomes 1 and 5 also decreased blood pressure, protein excretion, and albumin excretion. These studies also identified several chromosomes in male (6, 11, Y) and female ( 4 , 6 , 11 , 19 , 20 ) rats that reduced albuminuria without altering blood pressure. These data indicate that genes contributing to salt-sensitive hypertension are found on multiple chromosomes of the Dahl SS/Mcwi rat. Furthermore, this consomic rat panel provides a stable genetic platform that can facilitate further gene mapping by either linkage studies or the breeding of congenic and subcongenic rats.

APA, Harvard, Vancouver, ISO, and other styles

20

Pai, Amrita V., Taylor Maddox, and Kathryn Sandberg. "T Cells and Hypertension: Solved and Unsolved Mysteries Regarding the Female Rat." Physiology 33, no. 4 (July 1, 2018): 254–60. http://dx.doi.org/10.1152/physiol.00011.2018.

Full text

Abstract:

T-cell function in female animal models of hypertension is poorly understood since most research is conducted in males. Our findings in Dahl-salt-sensitive and Dahl salt-resistant rats support prior research showing sex-specific T-cell effects in the pathophysiology of hypertension. Further studies are needed to inform clinical studies in both sexes and to provide clues into immune mechanisms underlying susceptibility and resilience to developing hypertension and associated disease.

APA, Harvard, Vancouver, ISO, and other styles

21

RUDD, M. "DAHL salt-resistant rat becomes salt-sensitive with inducible nitric oxide synthase inhibition." American Journal of Hypertension 10, no. 4 (April 1997): 20A. http://dx.doi.org/10.1016/s0895-7061(97)88712-2.

Full text

APA, Harvard, Vancouver, ISO, and other styles

22

Churchill, P. C., M. C. Churchill, and A. K. Bidani. "Kidney cross transplants in Dahl salt-sensitive and salt-resistant rats." American Journal of Physiology-Heart and Circulatory Physiology 262, no. 6 (June 1, 1992): H1809—H1817. http://dx.doi.org/10.1152/ajpheart.1992.262.6.h1809.

Full text

Abstract:

Previous kidney cross-transplant studies have demonstrated that the genotype of the kidney plays a role in determining the blood pressure of the recipient in Dahl salt-sensitive (S) and salt-resistant (R) rats. The present studies were designed to elucidate this role. Kidney cross transplants were performed in unilaterally nephrectomized male recipients (John Rapp strains), such that each rat had a native kidney and a transplanted kidney of the opposite genotype. S and R rats with a native kidney and a transplanted kidney of the same genotype served as controls. After 4 wk on a 7.8% NaCl diet, rats were anesthetized and renal clearance studies were performed. S kidneys had lower glomerular filtration rate (GFR) and renal plasma flow (RPF) than R kidneys, and these differences were determined by the kidney's genotype rather than the recipient's, since S kidneys in R recipients tended to have lower GFR and RPF than R kidneys in S recipients. In contrast, independent of the kidney's genotype, the kidneys in S rats tended to have higher fractional excretion of H2O and Na (FEH2O and FENa) than the kidneys in R rats. Thus there were genetically determined differences in renal function between S and R rats; some (RPF and GFR) were intrinsic to the kidney, whereas others (FEH2O and FENa) were intrinsic to the host.(ABSTRACT TRUNCATED AT 250 WORDS)

APA, Harvard, Vancouver, ISO, and other styles

23

Huang, Bing S., Roselyn A. White, Li Bi, and Frans H. H. Leenen. "Central infusion of aliskiren prevents sympathetic hyperactivity and hypertension in Dahl salt-sensitive rats on high salt intake." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 302, no. 7 (April 1, 2012): R825—R832. http://dx.doi.org/10.1152/ajpregu.00368.2011.

Full text

Abstract:

Central infusion of an angiotensin type 1 (AT1) receptor blocker prevents sympathetic hyperactivity and hypertension in Dahl salt-sensitive (S) rats on high salt. In the present study, we examined whether central infusion of a direct renin inhibitor exerts similar effects. Intracerebroventricular infusion of aliskiren at the rate of 0.05 mg/day markedly inhibited the increase in ANG II levels in the cerebrospinal fluid and in blood pressure (BP) caused by intracerebroventricular infusion of rat renin. In Dahl S rats on high salt, intracerebroventricular infusion of aliskiren at 0.05 and 0.25 mg/day for 2 wk similarly decreased resting BP in Dahl S rats on high salt. In other groups of Dahl S rats, high salt intake for 2 wk increased resting BP by ∼25 mmHg, enhanced pressor and sympathoexcitatory responses to air-stress, and desensitized arterial baroreflex function. All of these effects were largely prevented by intracerebroventricular infusion of aliskiren at 0.05 mg/day. Aliskiren had no effects in rats on regular salt. Neither high salt nor aliskiren affected hypothalamic ANG II content. These results indicate that intracerebroventricular infusions of aliskiren and an AT1 receptor blocker are similarly effective in preventing salt-induced sympathetic hyperactivity and hypertension in Dahl S rats, suggesting that renin in the brain plays an essential role in the salt-induced hypertension. The absence of an obvious increase in hypothalamic ANG II by high salt, or decrease in ANG II by aliskiren, suggests that tissue levels do not reflect renin-dependent ANG II production in sympathoexcitatory angiotensinergic neurons.

APA, Harvard, Vancouver, ISO, and other styles

24

Karlsen, Finn M., Paul P. Leyssac, and Niels-Henrik Holstein-Rathlou. "Tubuloglomerular feedback in Dahl rats." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 274, no. 6 (June 1, 1998): R1561—R1569. http://dx.doi.org/10.1152/ajpregu.1998.274.6.r1561.

Full text

Abstract:

We have previously demonstrated a loss of autoregulation in Dahl salt-sensitive (Dahl-S) rats rendered hypertensive on a high-salt diet. To determine whether this was due to a decreased activity of either the myogenic or the tubuloglomerular feedback (TGF) response, we tested the TGF response in both Dahl-S and salt-resistant Dahl rats on high- and low-salt diets. TGF was investigated in the closed-loop mode with a videometric technique, in which the response in late proximal flow rate to perturbations in Henle flow rate was measured. All Dahl rats showed a similar compensatory response to perturbations around the natural operating point, with a TGF response that was more efficient than in normotensive Sprague-Dawley rats. No evidence of decreased TGF responsiveness in hypertensive Dahl-S rats was found. The results suggest that the loss of autoregulation in hypertensive Dahl-S rats is due to a compromised myogenic response. We also measured the free-flow proximal intratubular pressure in Dahl rats. Perfectly regular oscillations were demonstrated in all Dahl series, including the hypertensive Dahl-S rats. This is the first demonstration of regular oscillations in an experimental rat model of hypertension.

APA, Harvard, Vancouver, ISO, and other styles

25

Wilson, Thomas W., Magdalena Alonso-Galicia, and Richard J. Roman. "Effects of Lipid-Lowering Agents in the Dahl Salt-Sensitive Rat." Hypertension 31, no. 1 (January 1998): 225–31. http://dx.doi.org/10.1161/01.hyp.31.1.225.

Full text

APA, Harvard, Vancouver, ISO, and other styles

26

Sawyer, R. Taylor, Elizabeth R. Flynn, Zachary M. Hutchens, Jan M. Williams, Michael R. Garrett, and Christine Maric-Bilkan. "Renoprotective effects of C-peptide in the Dahl salt-sensitive rat." American Journal of Physiology-Renal Physiology 303, no. 6 (September 15, 2012): F893—F899. http://dx.doi.org/10.1152/ajprenal.00068.2012.

Full text

Abstract:

Previous studies have demonstrated that renoprotective effects of C-peptide in experimental models of diabetes-induced renal disease may be mediated via lowering blood glucose. The present study examined the renoprotective effects of C-peptide in a model of nondiabetic renal disease, the Dahl salt-sensitive (SS/jr) rat. SS/jr rats were placed on a 2% NaCl diet for 2 wk (HS2, resulting in mild to moderate renal injury) or 4 wk (HS4, resulting in advanced renal injury) and then received either vehicle (veh) or C-peptide (Cpep) for additional 4 wk. Urine albumin (UAE) and protein (UPE) excretion rates were measured at baseline (i.e., before initiation of veh or Cpep treatment) and 4 wk later (i.e., at the time of death). Glomerular permeability, indexes of glomerulosclerosis and tubulointerstitial fibrosis, the presence of inflammatory cells, and protein expression of transforming growth factor-β (TGF-β) and podocin were measured at the time of death. In HS2 + veh rats, UAE and UPE increased by 74 and 92%, respectively, from baseline and the time of death. While HS2 + Cpep attenuated this increase in UAE and UPE, HS4 + Cpep had no effect on these parameters. Similarly, HS2 + Cpep reduced glomerular permeability, tubulointerstitial fibrosis, renal inflammation, TGF-β, and podocin protein expression, while HS4 + Cpep had no effect. These studies indicate that C-peptide is renoprotective in nondiabetic experimental models with mild to moderate renal injury.

APA, Harvard, Vancouver, ISO, and other styles

27

Tawar, Urmila, Kumar Kotlo, Shilpa Jain, Sagar Shukla, Suman Setty, and Robert S. Danziger. "Renal Phosphodiesterase 4B Is Activated in the Dahl Salt-Sensitive Rat." Hypertension 51, no. 3 (March 2008): 762–66. http://dx.doi.org/10.1161/hypertensionaha.107.105387.

Full text

APA, Harvard, Vancouver, ISO, and other styles

28

Onwochei, M. O., and J. P. Rapp. "Hyposecretion of atrial natriuretic factor by prehypertensive Dahl salt-sensitive rat." Hypertension 13, no. 5 (May 1989): 440–48. http://dx.doi.org/10.1161/01.hyp.13.5.440.

Full text

APA, Harvard, Vancouver, ISO, and other styles

29

Gomez-Sanchez, Elise P., Jacqueline Samuel, Gaston Vergara, and Naveed Ahmad. "Effect of 3β-hydroxysteroid dehydrogenase inhibition by trilostane on blood pressure in the Dahl salt-sensitive rat." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 288, no. 2 (February 2005): R389—R393. http://dx.doi.org/10.1152/ajpregu.00441.2004.

Full text

Abstract:

The brains of rats and humans express the enzymes required for the synthesis of aldosterone from cholesterol, including the 3β-steroid dehydrogenase that catalyzes the conversion of pregnenolone to progesterone in the pathway of adrenal steroid synthesis. Salt-induced hypertension in the Dahl inbred salt-sensitive (SS/jr) rat is associated with normal to low levels of circulating aldosterone, yet it is abrogated by the central infusion of mineralocorticoid receptor antagonists. To test the hypothesis that de novo synthesis of aldosterone in the brain has a pathophysiological role in the salt-induced hypertension of the SS rat, the 3β-steroid dehydrogenase antagonist trilostane was infused continuously intracerebroventricularly or subcutaneously in two different cohorts of Dahl SS/jr rats, one female, the other male, during and after the development of salt-induced hypertension. The doses of trilostane used had no effect on blood pressure when infused subcutaneously. Animals receiving vehicle intracerebroventricularly experienced a 30- to 45-mmHg increase in systolic blood pressure measured by tail cuff. The intracerebroventricular, but not subcutaneous, infusion of 0.3 μg/h trilostane effectively blocked the increase in systolic blood pressure and reversed the hypertension produced by drinking 0.9% saline. Trilostane was equally effective in female and male rats. Weight gain, serum aldosterone and corticosterone concentrations, and behavior assessed subjectively and by elevated plus maze were unchanged by the trilostane treatment. These studies suggest that the synthesis in the brain of a mineralocorticoid receptor agonist, probably aldosterone, is responsible in part for the salt-induced hypertension of the inbred Dahl SS/jr rat.

APA, Harvard, Vancouver, ISO, and other styles

30

GARRETT, MICHAEL R., YASSER SAAD, HOWARD DENE, and JOHN P. RAPP. "Blood pressure QTL that differentiate Dahl salt-sensitive and spontaneously hypertensive rats." Physiological Genomics 3, no. 1 (June 29, 2000): 33–38. http://dx.doi.org/10.1152/physiolgenomics.2000.3.1.33.

Full text

Abstract:

Garrett, Michael R., Yasser Saad, Howard Dene, and John P. Rapp. Blood pressure QTL that differentiate Dahl salt-sensitive and spontaneously hypertensive rats. Physiol Genomics 3: 33–38, 2000.—Our purpose was to define quantitative trait loci (QTL) for blood pressure that differ between two widely used hypertensive rat strains, the Dahl salt-sensitive (S) rat and the spontaneously hypertensive rat (SHR). A genome scan was done on an F2 (S × SHR) population fed 8% NaCl for 4 wk. Three blood pressure QTL were detected, one on each of rat chromosomes (chr) 3, 8, and 9. For the chr 3 QTL the SHR allele increased blood pressure, and for chr 8 and 9 the S allele increased blood pressure. The QTL on chr 9 was exceptionally strong, having a LOD score of 7.3 and accounting for 30% of the phenotypic variance and a difference of 40 mmHg between homozygotes. A review of the literature in conjunction with the present data suggests that S and SHR are not different for the previously described prominent blood pressure QTL on chr 1, 2, 10, and 13. QTL for body weight on chr 4, 12, 18, and 20, each with an effect of about 30 g, were incidentally observed.

APA, Harvard, Vancouver, ISO, and other styles

31

Kotchen, T. A., C. E. Ott, S. A. Whitescarver, L. M. Resnick, J. M. Gertner, and N. G. Blehschmidt. "Calcium and Calcium Regulating Hormones in the "Prehypertensive" Dahl Salt Sensitive Rat (Calcium and Salt Sensitive Hypertension)." American Journal of Hypertension 2, no. 10 (October 1, 1989): 747–53. http://dx.doi.org/10.1093/ajh/2.10.747.

Full text

APA, Harvard, Vancouver, ISO, and other styles

32

Nakazawa, Yusuke, Shinya Inoue, Yuka Nakamura, Yasuo Iida, Yasuhito Ishigaki, and Katsuhito Miyazawa. "High‐salt diet promotes crystal deposition through hypertension in Dahl salt‐sensitive rat model." International Journal of Urology 26, no. 8 (June 30, 2019): 839–46. http://dx.doi.org/10.1111/iju.14035.

Full text

APA, Harvard, Vancouver, ISO, and other styles

33

Durand, Matthew J., Carol Moreno, Andrew S. Greene, and Julian H. Lombard. "Impaired relaxation of cerebral arteries in the absence of elevated salt intake in normotensive congenic rats carrying the Dahl salt-sensitive renin gene." American Journal of Physiology-Heart and Circulatory Physiology 299, no. 6 (December 2010): H1865—H1874. http://dx.doi.org/10.1152/ajpheart.00700.2010.

Full text

Abstract:

This study evaluated endothelium-dependent vascular relaxation in response to acetylcholine (ACh) in isolated middle cerebral arteries (MCA) from Dahl salt-sensitive (Dahl SS) rats and three different congenic strains that contain a portion of Brown Norway (BN) chromosome 13 introgressed onto the Dahl SS genetic background through marker-assisted breeding. Two of the congenic strains carry a 3.5-Mbp portion and a 2.6-Mbp portion of chromosome 13 that lie on opposite sides of the renin locus, while the third contains a 2.0-Mbp overlapping region that includes the BN renin allele. While maintained on a normal salt (0.4% NaCl) diet, MCAs from Dahl SS rats and the congenic strains retaining the Dahl SS renin allele failed to dilate in response to ACh, whereas MCAs from the congenic strain carrying the BN renin allele exhibited normal vascular relaxation. In congenic rats receiving the BN renin allele, vasodilator responses to ACh were eliminated by nitric oxide synthase inhibition with NG-nitro-l-arginine methyl ester, angiotensin-converting enzyme inhibition with captopril, and AT1 receptor blockade with losartan. NG-nitro-l-arginine methyl ester-sensitive vasodilation in response to ACh was restored in MCAs of Dahl SS rats that received either a 3-day infusion of a subpressor dose of angiotensin II (3 ng·kg−1·min−1 iv), or chronic treatment with the superoxide dismutase mimetic tempol (15 mg·kg−1·day−1). These findings indicate that the presence of the Dahl SS renin allele plays a crucial role in endothelial dysfunction present in the cerebral circulation of the Dahl SS rat, even in the absence of elevated dietary salt intake, and that introgression of the BN renin allele rescues endothelium-dependent vasodilator responses by restoring normal activation of the renin-angiotensin system.

APA, Harvard, Vancouver, ISO, and other styles

34

Buss, Sebastian J., Johannes Backs, Michael M. Kreusser, Stefan E. Hardt, Christiane Maser-Gluth, Hugo A. Katus, and Markus Haass. "Spironolactone Preserves Cardiac Norepinephrine Reuptake in Salt-Sensitive Dahl Rats." Endocrinology 147, no. 5 (May 1, 2006): 2526–34. http://dx.doi.org/10.1210/en.2005-1167.

Full text

Abstract:

An impairment of cardiac norepinephrine (NE) reuptake via the neuronal NE transporter (NET) enhances the effects of increased cardiac NE release in heart failure patients. Increasing evidence suggests that aldosterone and endothelins promote sympathetic overstimulation of failing hearts. Salt-sensitive Dahl rats (DS) fed a high-salt diet developed arterial hypertension and diastolic heart failure as well as elevated plasma levels of endothelin-1 and NE. Cardiac NE reuptake and NET-binding sites, as assessed by clearance of bolus-injected [3H]NE in isolated perfused rat hearts and [3H]mazindol binding, were reduced. Treatment of DS with the mineralocorticoid receptor antagonist spironolactone preserved the plasma levels of endothelin-1 and NE, cardiac NE reuptake, and myocardial NET density. Moreover, the ventricular function and survival of spironolactone-treated DS were significantly improved compared with untreated DS. The α1-inhibitor prazosin decreased blood pressure in DS similar to spironolactone treatment, but did not normalize the plasma levels of endothelin-1 and NE, NE reuptake, or ventricular function. In a heart failure-independent model, Wistar rats that were infused with aldosterone and fed a high-salt diet developed impaired cardiac NE reuptake. Treatment of these rats with the endothelin A receptor antagonist darusentan attenuated the impairment of NE reuptake. In conclusion, spironolactone preserves NET-dependent cardiac NE reuptake in salt-dependent heart failure. Evidence is provided that aldosterone inhibits NET function through an interaction with the endothelin system. Selective antagonism of the mineralocorticoid and/or the endothelin A receptor might represent therapeutic principles to prevent cardiac sympathetic overactivity in salt-dependent heart failure.

APA, Harvard, Vancouver, ISO, and other styles

35

Shehata, Marlene F. "Article Commentary: The Alternatively Spliced Form “b” of the Epithelial Sodium Channel α subunit (α ENaC): Any Prior Evidence of its Existence?" Clinical Medicine Insights: Cardiology 4 (January 2010): CMC.S5270. http://dx.doi.org/10.4137/cmc.s5270.

Full text

Abstract:

The epithelial sodium channel (ENaC) is critical in maintaining sodium balance across aldosterone-responsive epithelia. ENaC is a combined channel formed of three subunits (αβγ) with α ENaC subunit being the most critical for channel functionality. In a previous report, we have demonstrated the existence and mRNA expression levels of four alternatively spliced forms of the α ENaC subunit denoted by -a, -b, -c and -d in kidney cortex of Dahl S and R rats. Of the four alternatively spliced forms presently identified, α ENaC-b is considered the most interesting for the following reasons: Aside from being a salt-sensitive transcript, α ENaC-b mRNA expression is ~32 fold higher than α ENaC wildtype in kidney cortex of Dahl rats. Additionally, the splice site used to generate α ENaC-b is conserved across species. Finally, α ENaC-b mRNA expression is significantly higher in salt-resistant Dahl R rats versus salt-sensitive Dahl S rats. As such, this commentary aims to highlight some of the previously published research articles that described the existence of an additional protein band on α ENaC western blots that could account for α ENaC-b in other rat species.

APA, Harvard, Vancouver, ISO, and other styles

36

Mattson, David L., Mary Pat Kunert, Mary L. Kaldunski, Andrew S. Greene, Richard J. Roman, Howard J. Jacob, and Allen W. Cowley. "Influence of diet and genetics on hypertension and renal disease in Dahl salt-sensitive rats." Physiological Genomics 16, no. 2 (January 15, 2004): 194–203. http://dx.doi.org/10.1152/physiolgenomics.00151.2003.

Full text

Abstract:

Experiments examined the influence of diet and genetics on hypertension and renal disease in inbred Dahl salt-sensitive (SS/Mcw) rats and consomic rats in which chromosomes 16 (SS.BN16) or 18 (SS.BN18) of the normotensive Brown Norway rat were inserted into the genetic background of the SS/Mcw. Dahl SS/Mcw breeders and offspring were randomly placed on a purified AIN-76A diet or a grain-based diet, and male offspring were screened for cardiovascular and renal phenotypes following 3 wk on a 4.0% NaCl diet. High-salt arterial blood pressure (162 ± 5 mmHg, n = 10), urinary protein excretion (147 ± 16 mg/day, n = 14), and albumin excretion (72 ± 9 mg/day, n = 14) were significantly elevated in the Dahl SS/Mcw maintained on the purified diet compared with rats fed the grain-based diet. Rats fed the purified diet also exhibited significantly more renal glomerular and tubular damage than rats fed the grain diet. Moreover, feeding the purified diet to the parents led to a significant increase in blood pressure in the offspring, regardless of offspring diet. Similar dietary effects were observed in SS.BN16 and SS.BN18 rats. In rats fed the purified diet, substitution of chromosomes 16 or 18 led to a significant decrease in arterial blood pressure, albumin excretion, and protein excretion compared with the SS/Mcw. Chromosomal substitution did not, however, affect albumin or protein excretion in the consomic rats compared with the SS/Mcw when the rats were maintained on the grain diet. These data demonstrate a significant influence of diet composition on salt-induced hypertension and renal disease in the Dahl SS/Mcw rat.

APA, Harvard, Vancouver, ISO, and other styles

37

Wu, Fei, Guanjong Chen, Aihua Zhang, Yang Yu, Minhua Fan, and Chaoshu Tang. "Renal Urotensin II System Plays Roles in the Regulation of Blood Pressure in Dahl Salt-Resistant Rat." International Journal of Hypertension 2016 (2016): 1–11. http://dx.doi.org/10.1155/2016/9146870.

Full text

Abstract:

Introduction. Dahl salt-resistant (SR) animal models are similar to peritoneal dialysis patients with fluid volumes overload with normal blood pressure in hemodynamic profiles. We will verify the roles of UII in the regulation of blood pressure in these animal models.Methodology. The Dahl salt-sensitive (SS) and SR rats and UII receptor gene knocked out (KO) mice were placed on a high-salt diet. Renal tissues were performed for the expression of UII in Dahl groups.Results. After high-salt diet for 6 weeks, the systolic blood pressure (SBP) in SR group was significantly lower, accompanied with higher urinary UII levels, higher 24-hour urinary sodium excretion, and higher urinary creatinine clearance in the SR rats in comparison to SS group. The expressions of UII and UT were both upregulated in the kidney tissues of SR group in comparison to SS group (P<0.05). After high-salt diet for 8 weeks, the SBP of the KO group is significantly higher than that of the wild type group.Conclusion. We first demonstrate that renal UII system can play important roles in the regulation of blood pressure in Dahl SR rats which can be highly correlated to its effect on renal tubular sodium absorption.

APA, Harvard, Vancouver, ISO, and other styles

38

Gomez-Sanchez, Elise P., Clara M. Gomez-Sanchez, Maria Plonczynski, and Celso E. Gomez-Sanchez. "Aldosterone synthesis in the brain contributes to Dahl salt-sensitive rat hypertension." Experimental Physiology 95, no. 1 (December 15, 2009): 120–30. http://dx.doi.org/10.1113/expphysiol.2009.048900.

Full text

APA, Harvard, Vancouver, ISO, and other styles

39

Hoagland, Kimberly M., Averia K. Flasch, Annette J. Dahly-Vernon, Elisabete Alcantara dos Santos, Mark A. Knepper, and Richard J. Roman. "Elevated BSC-1 and ROMK Expression in Dahl Salt-Sensitive Rat Kidneys." Hypertension 43, no. 4 (April 2004): 860–65. http://dx.doi.org/10.1161/01.hyp.0000120123.44945.47.

Full text

APA, Harvard, Vancouver, ISO, and other styles

40

Rowland, N. E., and M. J. Fregly. "Role of Gonadal Hormones in Hypertension in the Dahl Salt-Sensitive Rat." Clinical and Experimental Hypertension. Part A: Theory and Practice 14, no. 3 (January 1992): 367–75. http://dx.doi.org/10.3109/10641969209036195.

Full text

APA, Harvard, Vancouver, ISO, and other styles

41

Jo, Chor Ho, Sua Kim, Il Hwan Oh, Joon-Sung Park, and Gheun-Ho Kim. "Alteration of Tight Junction Protein Expression in Dahl Salt-Sensitive Rat Kidney." Kidney and Blood Pressure Research 42, no. 6 (2017): 951–60. http://dx.doi.org/10.1159/000485332.

Full text

APA, Harvard, Vancouver, ISO, and other styles

42

Steele, T. H., and L. Challoner-Hue. "Influence of salt on response to nitrendipine by Dahl rat kidney." American Journal of Physiology-Renal Physiology 252, no. 3 (March 1, 1987): F487—F490. http://dx.doi.org/10.1152/ajprenal.1987.252.3.f487.

Full text

Abstract:

We examined the responses to the calcium channel blocker, nitrendipine, of isolated perfused kidneys from Dahl salt-sensitive (DS) and salt-resistant (DR) rats that had been stabilized on high- and low-NaCl diets. Blood pressures of high-salt DS rats exceeded those of the other three groups. After norepinephrine vasoconstriction sufficient to increase renal vascular resistance (RVR) by 50%, the superimposition of 10(-5) M nitrendipine increased the glomerular filtration rate (GFR) of high-salt DS rat kidneys by 125% over control values but returned the GFR of high-salt DR kidneys only to control. Nitrendipine superimposition increased the GFR of low-salt DS and DR rat kidneys by 124 and 40% over control values, respectively, and partially restored the RVR toward control. Nitrendipine alone, without norepinephrine, did not affect the GFR or RVR. The persistence within the DS kidney of an exaggerated glomerular circulatory “rebound” response to nitrendipine following the development of hypertension suggests the possibility of a maladaptation of DS kidney cell calcium regulation. The DR kidney manifests a similar response during salt restriction, but this disappears on a high-NaCl diet.

APA, Harvard, Vancouver, ISO, and other styles

43

Spradley, Frank T., Dao H. Ho, and Jennifer S. Pollock. "Dahl SS rats demonstrate enhanced aortic perivascular adipose tissue-mediated buffering of vasoconstriction through activation of NOS in the endothelium." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 310, no. 3 (February 1, 2016): R286—R296. http://dx.doi.org/10.1152/ajpregu.00469.2014.

Full text

Abstract:

Perivascular adipose tissue (PVAT) mediates buffering of vasoconstriction through activation of endothelium-derived factors. We hypothesized that the PVAT of Dahl salt-sensitive (Dahl SS) rats has reduced ability to buffer vasoconstriction. Vascular reactivity experiments were performed on aortic rings with PVAT intact (+PVAT) or removed (−PVAT), and endothelium intact (+ENDO) or removed (−ENDO) from Dahl SS rats and control SS.13BNrats (Dahl SS rats that have had chromosome 13 completely replaced with that of the Brown Norway rat, rendering this strain insensitive to high-salt or high-fat diet-induced hypertension). Endothelial dysfunction, assessed by ACh-mediated vasorelaxation, was confirmed in aortic rings of Dahl SS rats. The +PVAT+ENDO aortic rings had indistinguishable phenylephrine-induced vasoconstriction between genotypes. In both strains, removal of PVAT significantly enhanced vasoconstriction. Dahl SS rat −PVAT+ENDO aortic rings displayed exaggerated vasoconstriction to phenylephrine vs. SS.13BNrats, indicating that PVAT-mediated buffering of vasoconstriction was greater in Dahl SS rats. Removal of both the ENDO and PVAT restored vasoconstriction in both strains. The nitric oxide synthase (NOS) inhibitor, Nω-nitro-l-arginine methyl ester (l-NAME), produced a similar effect as that seen with −ENDO. These data indicate that the function of the PVAT to activate endothelium-derived NOS is enhanced in Dahl SS compared with SS.13BNrats and, most likely, occurs through a pathway that is distinct from ACh-mediated activation of NOS. PVAT weight and total PVAT leptin levels were greater in Dahl SS rats. Leptin induced a significantly decreased vasoconstriction in −PVAT+ENDO aortic rings from Dahl SS rats, but not SS.13BNrats. In contrast to our initial hypothesis, PVAT in Dahl SS rats buffers vasoconstriction by activating endothelial NOS via mechanisms that may include the involvement of leptin. Thus, the PVAT serves a vasoprotective role in Dahl SS rats on normal-salt diet.

APA, Harvard, Vancouver, ISO, and other styles

44

Ray, Sarah C., Bansari Patel, Debra L. Irsik, Jingping Sun, Hiram Ocasio, Gene R. Crislip, Chunhua H. Jin, et al. "Sodium bicarbonate loading limits tubular cast formation independent of glomerular injury and proteinuria in Dahl salt-sensitive rats." Clinical Science 132, no. 11 (June 15, 2018): 1179–97. http://dx.doi.org/10.1042/cs20171630.

Full text

Abstract:

Sodium bicarbonate (NaHCO3) slows the decline in kidney function in patients with chronic kidney disease (CKD), yet the mechanisms mediating this effect remain unclear. The Dahl salt-sensitive (SS) rat develops hypertension and progressive renal injury when fed a high salt diet; however, the effect of alkali loading on kidney injury has never been investigated in this model. We hypothesized that NaHCO3 protects from the development of renal injury in Dahl salt-sensitive rats via luminal alkalization which limits the formation of tubular casts, which are a prominent pathological feature in this model. To examine this hypothesis, we determined blood pressure and renal injury responses in Dahl SS rats drinking vehicle (0.1 M NaCl) or NaHCO3 (0.1 M) solutions as well as in Dahl SS rats lacking the voltage-gated proton channel (Hv1). We found that oral NaHCO3 reduced tubular NH4+ production, tubular cast formation, and interstitial fibrosis in rats fed a high salt diet for 2 weeks. This effect was independent of changes in blood pressure, glomerular injury, or proteinuria and did not associate with changes in renal inflammatory status. We found that null mutation of Hv1 also limited cast formation in Dahl SS rats independent of proteinuria or glomerular injury. As Hv1 is localized to the luminal membrane of TAL, our data suggest that alkalization of the luminal fluid within this segment limits cast formation in this model. Reduced cast formation, secondary to luminal alkalization within TAL segments may mediate some of the protective effects of alkali loading observed in CKD patients.

APA, Harvard, Vancouver, ISO, and other styles

45

Moreno, Carol, Mary L. Kaldunski, Tao Wang, Richard J. Roman, Andrew S. Greene, Jozef Lazar, Howard J. Jacob, and Allen W. Cowley. "Multiple blood pressure loci on rat chromosome 13 attenuate development of hypertension in the Dahl S hypertensive rat." Physiological Genomics 31, no. 2 (October 2007): 228–35. http://dx.doi.org/10.1152/physiolgenomics.00280.2006.

Full text

Abstract:

Previous studies have indicated that substitution of chromosome 13 of the salt-resistant Brown Norway BN/SsNHsdMcwi (BN) rat into the genomic background of the Dahl salt-sensitive SS/JrHsdMcwi (SS) rat attenuates the development of salt-sensitive hypertension and renal damage. To identify the regions within chromosome 13 that attenuate the development of hypertension during a high-salt diet in the SS rat, we phenotyped a series of overlapping congenic lines covering chromosome 13, generated from an intercross between the consomic SS-13BN rat and the SS rat. Blood pressure was determined in chronically catheterized rats after 2 wk of high-salt diet (8% NaCl) together with microalbuminuria as an index of renal damage. Four discrete regions were identified, ranging in size from 4.5 to 16 Mbp, each of which independently provided significant protection from hypertension during high-salt diet, reducing blood pressure by 20–29 mmHg. Protection was more robust in female than male rats in some of the congenic strains, suggesting a sex interaction with some of the genes determining blood pressure during high-salt diet. Among the 23 congenic strains, several regions overlapped. When three of the “protective” regions were combined onto one broad congenic strain, no summation effect was seen, obtaining the same decrease in blood pressure as with each one independently. We conclude from these studies that there are four regions within chromosome 13 containing genes that interact epistatically and influence arterial pressure.

APA, Harvard, Vancouver, ISO, and other styles

46

Wellman, G. C., L. Cartin, D. M. Eckman, A. S. Stevenson, C. M. Saundry, W. J. Lederer, and M. T. Nelson. "Membrane depolarization, elevated Ca2+ entry, and gene expression in cerebral arteries of hypertensive rats." American Journal of Physiology-Heart and Circulatory Physiology 281, no. 6 (December 1, 2001): H2559—H2567. http://dx.doi.org/10.1152/ajpheart.2001.281.6.h2559.

Full text

Abstract:

Elevated intracellular Ca2+([Ca2+]i) has been implicated in contractile and phenotypic changes in arterial smooth muscle during hypertension. This study examined the role of membrane potential and [Ca2+]i in altered gene expression in cerebral arteries of a rat (Dahl) genetic model of salt-sensitive hypertension. Cerebral arteries from hypertensive animals (Dahl salt-sensitive) exhibited a tonic membrane depolarization of ∼15 mV compared with normotensive (Dahl salt-resistant) animals. Consistent with this membrane depolarization, voltage-dependent K+currents were decreased in cerebral artery myocytes isolated from hypertensive animals. Arterial wall Ca2+ was elevated in cerebral arteries from hypertensive animals, an effect reversed by diltiazem, a blocker of voltage-dependent Ca2+ channels. This depolarization-induced increase in [Ca2+]i was associated with increased activation of the transcription factor, cAMP response element binding protein, and increased expression of the immediate early gene c-fos, both of which are reversed by acute exposure to the voltage-dependent Ca2+ channel blocker nisoldipine. This study provides the first information linking altered Ca2+handling to changes in gene expression in cerebral arteries during hypertension.

APA, Harvard, Vancouver, ISO, and other styles

47

Lukaszewicz, Kathleen M., and Julian H. Lombard. "Role of the CYP4A/20-HETE pathway in vascular dysfunction of the Dahl salt-sensitive rat." Clinical Science 124, no. 12 (February 26, 2013): 695–700. http://dx.doi.org/10.1042/cs20120483.

Full text

Abstract:

20-HETE (20-hydroxyeicosatetraenoic acid), a vasoconstrictor metabolite of arachidonic acid formed through the action of CYP4A (cytochrome P450-4A) in vascular smooth muscle cells, has been implicated in the development of hypertension and vascular dysfunction. There have been a number of reports in human subjects demonstrating an association between elevated urinary excretion of 20-HETE and hypertension, as well as increased 20-HETE production and vascular dysfunction. The Dahl SS (salt-sensitive) rat is a genetic model of salt-sensitive hypertension that exhibits vascular dysfunction, even when maintained on a normal-salt diet and before the development of hypertension. This mini-review highlights our current research on the role of CYP4A and 20-HETE in the vascular dysfunction of the Dahl SS rat. In our studies, the SS rat is compared with the consomic SS-5BN rat, having chromosome 5 from the salt-resistant Brown Norway rat (carrying all CYP4A genes) introgressed on to the SS genetic background. Our laboratory has demonstrated restoration of normal vascular function in the SS rat with inhibition of the CYP4A/20-HETE pathway, suggesting a direct role for this pathway in the vascular dysfunction in this animal model. Our studies have also shown that the SS rat has an up-regulated CYP4A/20-HETE pathway within their cerebral vasculature compared with the SS-5BN consomic rat, which causes endothelial dysfunction through the production of ROS (reactive oxygen species). Our data shows that ROS influences the expression of the CYP4A/20-HETE pathway in the SS rat in a feed-forward mechanism whereby elevated ROS stimulates production of 20-HETE. The presence of this vicious cycle offers a possible explanation for the spiralling effects of elevated 20-HETE on the development of vascular dysfunction in this animal model.

APA, Harvard, Vancouver, ISO, and other styles

48

Kotchen, T. A., H. Y. Zhang, M. Covelli, and N. Blehschmidt. "Insulin resistance and blood pressure in Dahl rats and in one-kidney, one-clip hypertensive rats." American Journal of Physiology-Endocrinology and Metabolism 261, no. 6 (December 1, 1991): E692—E697. http://dx.doi.org/10.1152/ajpendo.1991.261.6.e692.

Full text

Abstract:

In normal rats, sucrose feeding results in insulin resistance and an elevation of arterial pressure. The purpose of this study was twofold: 1) to evaluate the effect of sucrose feeding on blood pressure in a genetic model and in an acquired model of hypertension and 2) to determine whether these models of hypertension are associated with insulin resistance. In Dahl salt-resistant (Dahl-R) rats on both a 0.45 and a 3% NaCl intake, systolic blood pressures were higher (P less than 0.01) in sucrose-drinking than in water-drinking animals. In contrast, blood pressure was not affected by dietary sucrose in Dahl salt-sensitive (Dahl-S) rats. Blood pressure was also not affected by sucrose in the one-kidney, one-clip (1K,1C) hypertensive rat. In response to an oral glucose load, serum glucose was similar in Dahl-R and Dahl-S rats, although serum insulin was higher (P less than 0.05) in Dahl-S rats, suggesting that Dahl-S rats are insulin resistant. In contrast, glucose and insulin responses were similar in hypertensive 1K,1C animals and normotensive controls. In conclusion, sucrose feeding increased blood pressure in Dahl-R but not in Dahl-S or 1K,1C hypertensive rats. Additionally, Dahl-S rats, but not hypertensive 1K,1C rats, are insulin resistant.

APA, Harvard, Vancouver, ISO, and other styles

49

Tayler, Hannah M., Jennifer C. Palmer, Taya L. Thomas, Patrick G. Kehoe, Julian FR Paton, and Seth Love. "Cerebral Aβ40 and systemic hypertension." Journal of Cerebral Blood Flow & Metabolism 38, no. 11 (August 7, 2017): 1993–2005. http://dx.doi.org/10.1177/0271678x17724930.

Full text

Abstract:

Mid-life hypertension and cerebral hypoperfusion may be preclinical abnormalities in people who later develop Alzheimer’s disease. Although accumulation of amyloid-beta (Aβ) is characteristic of Alzheimer’s disease and is associated with upregulation of the vasoconstrictor peptide endothelin-1 within the brain, it is unclear how this affects systemic arterial pressure. We have investigated whether infusion of Aβ40 into ventricular cerebrospinal fluid modulates blood pressure in the Dahl salt-sensitive rat. The Dahl salt-sensitive rat develops hypertension if given a high-salt diet. Intracerebroventricular infusion of Aβ induced a progressive rise in blood pressure in rats with pre-existing hypertension produced by a high-salt diet ( p < 0.0001), but no change in blood pressure in normotensive rats. The elevation in arterial pressure in high-salt rats was associated with an increase in low frequency spectral density in systolic blood pressure, suggesting autonomic imbalance, and reduced cardiac baroreflex gain. Our results demonstrate the potential for intracerebral Aβ to exacerbate hypertension, through modulation of autonomic activity. Present findings raise the possibility that mid-life hypertension in people who subsequently develop Alzheimer’s disease may in some cases be a physiological response to reduced cerebral perfusion complicating the accumulation of Aβ within the brain.

APA, Harvard, Vancouver, ISO, and other styles

50

Rudemiller, Nathan P., and David L. Mattson. "Candidate genes for hypertension: insights from the Dahl S rat." American Journal of Physiology-Renal Physiology 309, no. 12 (December 15, 2015): F993—F995. http://dx.doi.org/10.1152/ajprenal.00092.2015.

Full text

Abstract:

Human genetic linkage and association studies have nominated many genes as possible contributors to disease. Mutating or deleting these genes in a relevant disease model can validate their association with disease and potentially uncover novel mechanisms of pathogenesis. Targeted genetic mutagenesis has only recently been developed in the rat, and this technique has been applied in the Dahl salt-sensitive (S) rat to investigate human candidate genes associated with hypertension. This mini-review communicates the findings of these studies and displays how targeted genetic mutagenesis may contribute to the discovery of novel therapies for patients.

APA, Harvard, Vancouver, ISO, and other styles

Journal articles on the topic 'Dahl salt sensitive rat'

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles