Female Mice Are Resistant to Inward Remodeling of Parenchymal Arterioles Observed in Male Mice During Angiotensin II‐Induced Hypertension

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Laura C. Chambers ◽  
Janice M. Diaz-Otero ◽  
Ting-Chieh Yen ◽  
William F. Jackson ◽  
Anne M. Dorrance
Keyword(s):  
Angiotensin Ii ◽  
Male Mice ◽  
Female Mice ◽  
Induced Hypertension

Abstract P135: 2-methoxyestradiol Minimizes Angiotensin II-induced Hypertension and Renal Dysfunction in Ovariectomized Female and Intact Male Mice

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Ajeeth K Pingili ◽  
Shyamala Thirunavukkarasu ◽  
Nayaab S Khan ◽  
Akemi Katsurada ◽  
Dewan S Majid ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Renal Dysfunction ◽  
Organ Damage ◽  
Ang Ii ◽  
Male Mice ◽  
Intact Male ◽  
Female Mice ◽  
End Organ Damage ◽  
Induced Hypertension ◽  
Post Menopausal

Men and post-menopausal females are more prone to develop hypertension and renal dysfunction as compared to pre-menopausal females. It is well documented that in various experimental models of hypertension, the protection against hypertension in females is lost following ovariectomy (OVX). Recently we have shown that CYP1B1 protects against angiotensin II (Ang II)-induced hypertension and associated cardiovascular changes in female mice, most likely via production of 2-methoxyestradiol (2-ME). This study was conducted to determine if 2-ME reduces Ang II-induced hypertension, renal dysfunction and end organ damage in OVX female, and intact male mice. Treatment of OVX Cyp1b1 +/+ and Cyp1b1 -/- female mice with 2-ME (1.5 mg/kg/day i.p., for 2 weeks) reduced Ang II-induced increase in systolic blood pressure (SBP) (182±5.1 vs. 143± 2.4 mmHg, 179±6.4 vs. 140± 8.6 mmHg, P < 0.05, n= 5), water consumption, urine output and osmolality, and proteinuria (5.5±0.7 vs. 3.3±0.5 mg/24 hrs, 8.4±1.3 vs. 4.4 ±0.9 mg/24 hrs) respectively. 2-ME also reduced Ang II-induced increase in SBP (188±2.6 vs. 143± 2.7 mmHg, P < 0.05, n= 5) in intact male mice. 2-ME did not alter water consumption and urine osmolality, but reduced urine output and sodium excretion, and proteinuria (14.4±2.0 vs. 6.0±0.5 mg/24 hrs) in intact Cyp1b1 +/+ male mice. Treatment with 2-ME attenuated Ang II-induced end-organ damage (actin and collagen accumulation) in OVX Cyp1b1 +/+ and Cyp1b1 -/- female and Cyp1b1 +/+ male mice. 2-ME mitigated urinary excretion of angiotensinogen in OVX Cyp1b1 +/+ and Cyp1b1 -/- female mice infused with Ang II. These data suggest that 2-ME reduces Ang II- induced hypertension and associated renal dysfunction and end-organ damage in OVX Cyp1b1 +/+ and Cyp1b1 -/- female, and intact male mice. Therefore, 2-ME could serve as a therapeutic agent for treatment of hypertension and associated pathogenesis in post-menopausal females, and intact males.

scholarly journals 2-Methoxyestradiol Reduces Angiotensin II–Induced Hypertension and Renal Dysfunction in Ovariectomized Female and Intact Male Mice

Hypertension ◽  
2017 ◽  
Vol 69 (6) ◽  
pp. 1104-1112 ◽  
Author(s):  
Ajeeth K. Pingili ◽  
Karen N. Davidge ◽  
Shyamala Thirunavukkarasu ◽  
Nayaab S. Khan ◽  
Akemi Katsurada ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Renal Dysfunction ◽  
Male Mice ◽  
Intact Male ◽  
Induced Hypertension

Estrogen receptor-α mediates estrogen protection from angiotensin II-induced hypertension in conscious female mice

2007 ◽  
Vol 292 (4) ◽  
pp. H1770-H1776 ◽  
Author(s):  
Baojian Xue ◽  
Jaya Pamidimukkala ◽  
Dennis B. Lubahn ◽  
Meredith Hay
Keyword(s):  
Estrogen Receptor ◽  
Angiotensin Ii ◽  
Estrogen Receptor Α ◽  
Protective Role ◽  
Protective Effects ◽  
Pressor Effect ◽  
Ang Ii ◽  
Female Mice ◽  
Female Sex Hormones ◽  
Induced Hypertension

It has been shown that the female sex hormones have a protective role in the development of angiotensin II (ANG II)-induced hypertension. The present study tested the hypotheses that 1) the estrogen receptor-α (ERα) is involved in the protective effects of estrogen against ANG II-induced hypertension and 2) central ERs are involved. Blood pressure (BP) was measured in female mice with the use of telemetry implants. ANG II (800 ng·kg−1·min−1) was administered subcutaneously via an osmotic pump. Baseline BP in the intact, ovariectomized (OVX) wild-type (WT) and ERα knockout (ERαKO) mice was similar; however, the increase in BP induced by ANG II was greater in OVX WT (23.0 ± 1.0 mmHg) and ERαKO mice (23.8 ± 2.5 mmHg) than in intact WT mice (10.1 ± 4.5 mmHg). In OVX WT mice, central infusion of 17β-estradiol (E2; 30 μg·kg−1·day−1) attenuated the pressor effect of ANG II (7.0 ± 0.4 mmHg), and this protective effect of E2 was prevented by coadministration of ICI-182,780 (ICI; 1.5 μg·kg−1·day−1, 18.8 ± 1.5 mmHg), a nonselective ER antagonist. Furthermore, central, but not peripheral, infusions of ICI augmented the pressor effects of ANG II in intact WT mice (17.8 ± 4.2 mmHg). In contrast, the pressor effect of ANG II was unchanged in either central E2-treated OVX ERαKO mice (19.0 ± 1.1 mmHg) or central ICI-treated intact ERαKO mice (19.6 ± 1.6 mmHg). Lastly, ganglionic blockade on day 7 after ANG II infusions resulted in a greater reduction in BP in OVX WT, central ER antagonist-treated intact WT, central E2 + ICI-treated OVX WT, ERαKO, and central E2- or ICI-treated ERαKO mice compared with that in intact WT mice given just ANG II. Together, these data indicate that ERα, especially central expression of the ER, mediates the protective effects of estrogen against ANG II-induced hypertension.

scholarly journals 6β-Hydroxytestosterone, a Cytochrome P450 1B1 Metabolite of Testosterone, Contributes to Angiotensin II–Induced Hypertension and Its Pathogenesis in Male Mice

Hypertension ◽  
2015 ◽  
Vol 65 (6) ◽  
pp. 1279-1287 ◽  
Author(s):  
Ajeeth K. Pingili ◽  
Mehmet Kara ◽  
Nayaab S. Khan ◽  
Anne M. Estes ◽  
Zongtao Lin ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Angiotensin Ii ◽  
Male Mice ◽  
Cytochrome P450 1B1 ◽  
Induced Hypertension

scholarly journals 6β-Hydroxytestosterone, a metabolite of testosterone generated by CYP1B1, contributes to vascular changes in angiotensin II-induced hypertension in male mice

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Ajeeth K. Pingili ◽  
Brett L. Jennings ◽  
Kamalika Mukherjee ◽  
Wadah Akroush ◽  
Frank J. Gonzalez ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Male Mice ◽  
Vascular Changes ◽  
Induced Hypertension

scholarly journals Sex-Specific Modulation of Blood Pressure and the Renin-Angiotensin System by ACE (Angiotensin-Converting Enzyme) 2

Hypertension ◽  
2020 ◽  
Vol 76 (2) ◽  
pp. 478-487 ◽  
Author(s):  
Hong Ji ◽  
Aline M.A. de Souza ◽  
Bilkish Bajaj ◽  
Wei Zheng ◽  
Xie Wu ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Protein Expression ◽  
Renin Angiotensin System ◽  
Converting Enzyme ◽  
Male Mice ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Renin Angiotensin ◽  
Female Mice ◽  
Induced Hypertension

We showed ACE (angiotensin-converting enzyme) 2 is higher in the kidney of male compared with female mice. To further investigate this sex difference, we examined the role of ACE2 in Ang-[1–8] (angiotensin [1–8])–induced hypertension and regulation of the renin-angiotensin system in the kidney of WT (wild type) and Ace2 KO (knockout) mice. Mean arterial pressure rose faster in WT male than WT female mice after Ang-[1–8] infusion. This sex difference was attenuated in ACE2 KO mice. Ang-[1–8] infusion reduced glomerular AT1R (angiotensin type 1 receptor) binding in WT female mice by 30%, and deletion of Ace2 abolished this effect. In contrast, Ang-[1–8] infusion increased glomerular AT1R binding in WT male mice by 1.2-fold, and this effect of Ang-[1–8] persisted in Ace2 KO male mice (1.3-fold). ACE2 also had an effect on renal protein expression of the neutral endopeptidase NEP (neprilysin), the enzyme that catabolizes Ang-[1–10] (angiotensin [1–10]), the precursor of Ang-[1–8]. Ang-[1–8] infusion downregulated NEP protein expression by 20% in WT male, whereas there was a slight increase in NEP expression in WT female mice. Deletion of Ace2 resulted in lowered NEP expression after Ang-[1-8] infusion in both sexes. These findings suggest sex-specific ACE2 regulation of the renin-angiotensin system contributes to female protection from Ang-[1–8]–induced hypertension. These findings have ramifications for the current coronavirus disease 2019 (COVID-19) pandemic, especially in hypertension since ACE2 is the SARS-CoV-2 receptor and hypertension is a major risk factor for poor outcomes.

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