Differential effects of sex steroids in young and aged female mRen2.Lewis rats: A model of estrogen and salt-sensitive hypertension

Chappell, Mark C.; Westwood, Brian; Yamaleyeva, Liliya M.

doi:10.1016/j.genm.2008.03.007

Cited by 52 publications

(46 citation statements)

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“…We have shown previously that the slow pressor response to ANG II infusion is also independent of oxidative stress in female Sprague Dawley rats (15). Consistent with our data, Chappell and colleagues failed to obtain reductions in blood pressure with tempol in female mREN2 rats (2). Taken together, these data point to the lack of a role for oxidative stress in controlling blood pressure in female rats regardless of whether the hypertension is experimental or genetic.…”

Section: Discussionsupporting

confidence: 90%

Refractory blood pressure in female SHR to increased oxidative stress is not mediated by NO or by upregulation of renal antioxidant enzymes

Lopez‐Ruiz

Iliescu

Reckelhoff

2010

American Journal of Physiology-Regulatory, Integrative and Comp

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There is a sex difference in the blood pressure (BP) responses to prooxidants and antioxidants in the spontaneously hypertensive rat (SHR). In contrast to males, BP in female SHR does not decrease in response to antioxidants, such as tempol or apocynin, or increase in response to the prooxidant, molsidomine. Molsidomine decreases BP and increases expression of antioxidants in male Wistar-Kyoto rats (WKY), but not male SHR. The present study tested the hypothesis that the mechanism responsible for the lack of a pressor response to molsidomine in females is due to higher endogenous nitric oxide (NO) or to compensatory upregulation of renal antioxidant enzymes. Female SHR were treated with molsidomine in the presence or absence of nitro-L-arginine methyl ester (L-NAME) for 2 wk. Molsidomine increased nitrate/nitrite (NO(x)) and F2-isoprostane (F2-IsoP) excretion, whereas L-NAME reduced NO(x) but increased F-Isop. Molsidomine and L-NAME together further reduced NO(x) and increased F2-IsoP. Molsidomine alone had no effect on BP; L-NAME alone increased BP. The combination of molsidomine and L-NAME did not increase BP above L-NAME alone levels. Whole body and renal oxidative stress increased, while renal cortical Cu,Zn-SOD expression was downregulated and catalase was upregulated by molsidomine; glutathione peroxidase expression was unaffected. These data support our previous studies suggesting that BP in female SHR is independent of either increases or decreases in oxidative stress. The mechanisms responsible for the sex difference in BP response to increase or decrease of oxidative stress are not due to increased NO in females or to compensatory upregulation of antioxidant enzymes in response to increases in oxidants.

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Section: Discussionsupporting

confidence: 90%

Refractory blood pressure in female SHR to increased oxidative stress is not mediated by NO or by upregulation of renal antioxidant enzymes

Lopez‐Ruiz

Iliescu

Reckelhoff

2010

American Journal of Physiology-Regulatory, Integrative and Comp

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“…The data-mining technique used (6,14,42) revealed several correlations for the variables previously determined (16) and the ones for this particular study as discussed above. The Mas receptor mRNA was positively correlated with food intake and body weight.…”

Section: Systemic At1 Receptor Blockade Regulates Expression Of Brainmentioning

confidence: 86%

“…CSA illuminates the most covariant variables with respect to clustering, providing an alternative data-mining method comparable to PCA, without the need for specialized computer packages (6,14,42). A freely available Excel template that performs CSA for up to 100 variables for 4 groups of 15 subjects is available (http://en.wikipedia.org/wiki/Correlate_summation_analy-sis).…”

Section: Methodsmentioning

confidence: 99%

Long-term systemic angiotensin II type 1 receptor blockade regulates mRNA expression of dorsomedial medulla renin-angiotensin system components

Gilliam-Davis¹,

Gallagher²,

Payne

et al. 2011

Physiological Genomics

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Long-term systemic angiotensin II type 1 receptor blockade regulates mRNA expression of dorsomedial medulla renin-angiotensin system components. Physiol Genomics 43: 829 -835, 2011. First published May 3, 2011 doi:10.1152/physiolgenomics.00167.2010 rats, renin-angiotensin system (RAS) blockade for 1 yr with the angiotensin II type 1 (AT1) receptor blocker L-158,809 prevents age-related impairments in metabolic function, similar to transgenic rats with low glial angiotensinogen (Aogen). Brain RAS regulation may contribute to the benefits of long-term systemic AT1 antagonism. We assessed the mRNA of RAS components in the dorsomedial medulla of F344 rats at 3 (young; n ϭ 8) or 15 mo of age (old; n ϭ 7) and in rats treated from 3 to 15 mo of age with 20 mg/l of the AT1 receptor antagonist L-158,809 (OldϩL; n ϭ 6). Aogen and renin mRNA were lower in the young compared with old group. Angiotensin-converting enzyme (ACE) mRNA was lower in the old and OldϩL compared with the young group. ACE2 and neprilysin expression were significantly higher in OldϩL compared with young or old rats. AT1b, AT2, and Mas receptor mRNA were higher with treatment. Leptin receptor mRNA was lower in the old rats and this was prevented by L-158,809 treatment. Dual-specificity phosphatase 1 (DUSP1) mRNA was highest in the OldϩL group. Aggregate correlate summation revealed a positive relationship for Mas receptor mRNA with food intake. The findings provide evidence for regulation of dorsomedial medullary renin and Aogen mRNA during aging. Long-term AT1 receptor blockade increases the mRNA of the enzymes ACE2 and neprilysin and the MAS receptor, which could potentially shift the balance from ANG II to ANG-(1-7) and prevent age-related declines in the leptin receptor and its signaling pathway.angiotensinogen; Fischer 344 rats; leptin; aggregate correlate summation SYSTEMIC BLOCKADE OF the renin-angiotensin system (RAS) with angiotensin II type 1 (AT 1 ) receptor blockers or angiotensinconverting enzyme (ACE) inhibitors provides beneficial effects outside of the classic hemodynamic actions. RAS blockade improves many components of aging and reduces the onset of the metabolic syndrome and Type 2 diabetes (1,8,17,43). However, the precise mechanisms underlying the beneficial effects are not entirely known. During aging, there is a decline in the circulating (systemic) RAS, including angiotensin (ANG)-(1-7) (30), suggesting that the beneficial actions of RAS blockade are partly due to the suppression of ANG II in tissues. Many tissues and organs contain their own local RAS, including the kidney, heart, vessels, adrenal gland, pancreas, and brain (4, 25). Increased brain ANG II activates sympathetic outflow, inhibits the baroreflex, stimulates thirst, and contributes to neurogenic hypertension (25,36, 38). In rats with chronic renal failure, components of the brain RAS are upregulated, resulting in sympathetic overactivity and hypertension (29). Transgenic mice with increased production of brain ANG II developed hypertension and an increase in salt ...

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“…THE CONGENIC mRen (2).Lewis rat is a hypertensive strain that exhibits marked sex differences in blood pressure, cardiac function, and renal injury (7). The basis for male-female differences in the mRen (2).Lewis and other experimental models of hypertension likely reflects, in part, the influence of sex steroids on the renin-angiotensin-aldosterone system (RAAS) (4,13,27).…”

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confidence: 99%

Influence of estrogen depletion and salt loading on renal angiotensinogen expression in the mRen(2).Lewis strain

Cohen

Lindsey

Pirro

et al. 2010

American Journal of Physiology-Renal Physiology

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Influence of estrogen depletion and salt loading on renal angiotensinogen expression in the mRen(2).Lewis strain. Am J Physiol Renal Physiol 299: F35-F42, 2010. First published May 12, 2010 doi:10.1152/ajprenal.00138.2010.Lewis (mRen2) strain is an ANG II-dependent model of hypertension expressing marked sex differences in blood pressure and tissue injury that also exhibits estrogen and salt sensitivity. Because estrogen and salt influence angiotensinogen (AGT), circulating and renal expression of the protein were assessed in the mRen2 using a sensitive and specific ELISA. Hemizygous female and male mRen2 were placed on normal (1% NaCl, NS)-or high (8% NaCl, HS)-salt diets from 5 to 15 wk of age while a separate NS cohort was ovariectomized (OVX). The OVX mRen2 exhibited higher blood pressure (184 Ϯ 6 vs. 149 Ϯ 5 mmHg, n ϭ 6), a 16-fold increase in urinary AGT (uAGT) (0.2 Ϯ 0.02 vs. 0.01 Ϯ 0.01 g·kg Ϫ1 ·day Ϫ1 , P Ͻ 0.01), but no change in proteinuria (PROT). Excretion of AGT was correlated with blood pressure and PROT in the female groups. The HS diet led to higher blood pressure (224 Ϯ 8 mmHg), a 180-fold increase in uAGT (1.8 Ϯ 0.2 g·kg Ϫ1 ·day Ϫ1 ), and increased PROT (98 Ϯ 9 vs. 7 Ϯ 1 mg·kg Ϫ1 ·day Ϫ1 ). Compared with females, NS males expressed higher excretion of uAGT (3.0 Ϯ 0.4 g·kg Ϫ1 ·day Ϫ1 ) and PROT (32 Ϯ 5 mg·kg Ϫ1 ·day Ϫ1 ); both were increased eightfold with HS (uAGT: 23 Ϯ 3 g·kg Ϫ1 ·day Ϫ1 ; PROT: 285 Ϯ 28 mg·kg Ϫ1 ·day Ϫ1 ) without a change in blood pressure. Although uAGT was markedly higher in the OVX and HS groups, neither renal cortical AGT mRNA or protein expression was increased. Moreover, AGT release in cortical slices was similar for the NS and HS females. We conclude that the increase in uAGT with estrogen depletion or HS likely may be a biomarker for glomerular damage reflecting filtration of the circulating protein in the mRen2. angiotensin II; normal salt diet; high-salt diet

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Differential effects of sex steroids in young and aged female mRen2.Lewis rats: A model of estrogen and salt-sensitive hypertension

Abstract: These studies in hypertensive mRen2. Lewis rats underscored the influence of ovarian hormones on BP and tissue injury, as well as the plasticity of this response, apparently due to age and salt status.

Cited by 52 publications

References 52 publications

Refractory blood pressure in female SHR to increased oxidative stress is not mediated by NO or by upregulation of renal antioxidant enzymes

Refractory blood pressure in female SHR to increased oxidative stress is not mediated by NO or by upregulation of renal antioxidant enzymes

Long-term systemic angiotensin II type 1 receptor blockade regulates mRNA expression of dorsomedial medulla renin-angiotensin system components

Influence of estrogen depletion and salt loading on renal angiotensinogen expression in the mRen(2).Lewis strain

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