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

Yu Wang, Robin Shoemaker, David Powell, Wen Su, Sean Thatcher, Lisa A. Cassis

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

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. NEW & NOTEWORTHY MasR deficiency abolishes protection of female mice from obesity-induced hypertension. Male MasR-deficient obese mice have reduced blood pressure and declines in cardiac function. ANG-(1–7) infusion restores obesity-induced cardiac dysfunction of wild-type, but not MasR-deficient, male mice. MasR agonists may be cardioprotective in obese males and females.

Original languageEnglish
Pages (from-to)H459-H468
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume312
Issue number3
DOIs
StatePublished - Mar 2017

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health (NIH) Grant HL-073085 (to L. Cassis), through Cores supported by NIH Grant GM-103527 (to L. Cassis), and by an American Heart Association Grant (14PRE20380163).

Publisher Copyright:
© 2017 the American Physiological Society.

Keywords

  • Angiotensin-(1–7)
  • Hypertension
  • Obesity

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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