Angiotensin-1-7 (Ang-(1-7)) counteracts angiotensin II through effects at Mas receptors (MasR). We demonstrated that sexual dimorphism of obesity-hypertension was associated with dysregulated production of Ang-(1-7). However, the role of MasR in sexual dimorphism of obesity-hypertension has not been examined. MasR deficient mice have also been reported to exhibit deficits in cardiac function. In this study, we hypothesized that deficiency of the MasR would differentially regulate obesity-hypertension in male
versus
(
vs
) female mice. In addition, we quantified effects of MasR deficiency on cardiac function in obese male mice. Male and female
MasR
+/+
and
-/-
mice were fed a low fat (LF, 10%kcal) or high fat (HF, 60% kcal) diet for 16 weeks, and blood pressure was quantified by radiotelemetry. As demonstrated previously, male
MasR
+/+
mice (24 hr diastolic blood pressure, DBP: LF, 90 ± 3; HF, 96 ± 2 mmHg; P<0.05), but not females (LF, 85 ± 1; HF, 85 ± 2 mmHg), developed hypertension in response to HF feeding. MasR deficiency converted female HF-fed mice to an obesity-hypertension phenotype (DBP: 92 ± 1 mmHg; P<0.05). Surprisingly, male HF-fed
MasR
-/-
mice exhibited reduced DBP compared to HF-fed
MasR
+/+
males (90 ± 1
vs
96 ± 2 mmHg; P<0.05). To define mechanisms for reductions in DBP of HF-fed male
MasR
-/-
mice, we performed cardiac magnetic resonance (CMR) imaging in both genotypes at 1 month of HF feeding.
MasR
-/-
mice had significantly reduced ejection fraction (EF) compared to
MasR
+/+
mice at baseline (51.4 ± 2.5
vs
59.3 ± 2.1%; P<0.05) and after one month of HF-feeding (49.8 ± 2.4
vs
52.6 ± 1.9%; P<0.05). Further, CMR imaging demonstrated a thickening of the ventricle wall in
MasR
-/-
mice with 1 month of HF-feeding.
MasR
+/+
, but not
MasR
-/-
mice, exhibited diet-induced reductions in EF (by 16%; P<0.05) at 1 month of HF feeding, which were reversed by infusion of Ang-(1-7). These results demonstrate that MasR contributes to sexual dimorphism of obesity-hypertension. Ang-(1-7) protects females from obesity-hypertension through the MasR. In contrast, reductions in DBP in obese male mice with MasR deficiency may arise from deficits in cardiac function. These results suggest that MasR agonists may be effective therapies for obesity-associated cardiovascular conditions.
