Angiotensin-1-7 (Ang-(1-7)) acts at Mas receptors (MasR) to oppose effects of angiotensin II (AngII). Previous studies demonstrated that protection of female mice from obesity-induced hypertension was associated with increased systemic Ang-(1-7), while male obese hypertensive mice exhibited increased systemic AngII. 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 weeks. MasR deficiency had no effect on obesity. At baseline, male and female MasR-/- mice had reduced ejection fraction (EF) and fractional shortening (FS) than MasR+/+ mice. Male, but not female HF-fed MasR+/+ mice had increased systolic (SBP) and diastolic blood pressures (DBP) compared to LF-fed controls. In HF-fed females, MasR deficiency increased DBP compared to LF-fed controls. In contrast, male HF-fed MasR-/- mice had lower DBP than MasR+/+ mice. We quantified cardiac function after 1 month 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, which 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.
- Mas receptor
- cardiac function
- Copyright © 2016, American Journal of Physiology-Heart and Circulatory Physiology