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Differential effects of Mas receptor deficiency on cardiac function and blood pressure in obese male and female mice.

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Title: Differential effects of Mas receptor deficiency on cardiac function and blood pressure in obese male and female mice.
Authors: Yu Wang, Shoemaker, Robin, Powell, David, Wen Su, Thatcher, Sean, Cassis, Lisa
Source: American Journal of Physiology: Heart & Circulatory Physiology; Mar2017, Vol. 312 Issue 3, pH459-H468, 10p
Subject Terms: ANGIOTENSIN II, OBESITY, LABORATORY mice
Abstract: Angiotensin-(1-7) [ANG- (1-7)] acts at Mas receptors (MasR) to oppose effects of angiotensin II (ANG II). Previous studies demonstrated that protection of female mice from obesity-induced hypertension was associated with increased systemic ANG-(1-7), whereas male obese hypertensive mice exhibited increased systemic ANG II. We hypothesized that MasR deficiency (MasR-/-) augments obesity-induced hypertension in males and abolishes protection of females. Male and female wild-type (MasR+/+) and MasR-/- mice were fed a low-fat (LF) or high-fat (HF) diet for 16 wk. MasR deficiency had no effect on obesity. At baseline, male and female MasR-/- mice had reduced ejection fraction (EF) and fractional shortening than MasR+/+ mice. Male, but not female, HF-fed MasR+/+ mice had increased systolic and diastolic (DBP) blood pressures compared with LF-fed controls. In HF-fed females, MasR deficiency increased DBP compared with LF-fed controls. In contrast, male HF-fed MasR-/- mice had lower DBP than MasR+/+ mice. We quantified cardiac function after 1 mo of HF feeding in males of each genotype. HF-fed MasR-/- mice had higher left ventricular (LV) wall thickness than MasR+/+ mice. Moreover, MasR+/+, but not MasR-/-, mice displayed reductions in EF from HF feeding that were reversed by ANG-(1-7) infusion. LV fibrosis was reduced in HF-fed MasR+/+ but not MasR-/- ANG-(1-7)- infused mice. These results demonstrate that MasR deficiency promotes obesity-induced hypertension in females. In males, HF feeding reduced cardiac function, which was restored by ANG-(1-7) in MasR+/+ but not MasR-/- mice. MasR agonists may be effective therapies for obesity-associated cardiovascular conditions. [ABSTRACT FROM AUTHOR]
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Abstract:Angiotensin-(1-7) [ANG- (1-7)] acts at Mas receptors (MasR) to oppose effects of angiotensin II (ANG II). Previous studies demonstrated that protection of female mice from obesity-induced hypertension was associated with increased systemic ANG-(1-7), whereas male obese hypertensive mice exhibited increased systemic ANG II. We hypothesized that MasR deficiency (MasR<sup>-/-</sup>) augments obesity-induced hypertension in males and abolishes protection of females. Male and female wild-type (MasR<sup>+/+</sup>) and MasR<sup>-/-</sup> mice were fed a low-fat (LF) or high-fat (HF) diet for 16 wk. MasR deficiency had no effect on obesity. At baseline, male and female MasR<sup>-/-</sup> mice had reduced ejection fraction (EF) and fractional shortening than MasR<sup>+/+</sup> mice. Male, but not female, HF-fed MasR<sup>+/+</sup> mice had increased systolic and diastolic (DBP) blood pressures compared with LF-fed controls. In HF-fed females, MasR deficiency increased DBP compared with LF-fed controls. In contrast, male HF-fed MasR<sup>-/-</sup> mice had lower DBP than MasR<sup>+/+</sup> mice. We quantified cardiac function after 1 mo of HF feeding in males of each genotype. HF-fed MasR<sup>-/-</sup> mice had higher left ventricular (LV) wall thickness than MasR<sup>+/+</sup> mice. Moreover, MasR<sup>+/+</sup>, but not MasR<sup>-/-</sup>, mice displayed reductions in EF from HF feeding that were reversed by ANG-(1-7) infusion. LV fibrosis was reduced in HF-fed MasR<sup>+/+</sup> but not MasR<sup>-/-</sup> ANG-(1-7)- infused mice. These results demonstrate that MasR deficiency promotes obesity-induced hypertension in females. In males, HF feeding reduced cardiac function, which was restored by ANG-(1-7) in MasR<sup>+/+</sup> but not MasR<sup>-/-</sup> mice. MasR agonists may be effective therapies for obesity-associated cardiovascular conditions. [ABSTRACT FROM AUTHOR]
ISSN:03636135
DOI:10.1152/ajpheart.00498.2016