Abstract 317: Mas Receptor Deficiency Increases Blood Pressure Of Female Obese Mice

Abstract

Objective: We recently demonstrated that female mice were protected from high fat (HF) diet-induced obesity hypertension. Protection of females from obesity-hypertension was associated with an activation of angiotensin converting enzyme 2 (ACE2) in adipose tissue as well as increased plasma concentrations of the ACE2 product, angiotensin-(1-7) (Ang-(1-7)). Previous investigators demonstrated that antagonism of Mas receptors (MasR), receptors for Ang-(1-7)-induced blood pressure regulation, abolished protection of female spontaneously hypertensive rats from angiotensin II (AngII)-induced hypertension. Taken together, these results suggest that activation of MasR protects females from obesity-induced hypertension. We hypothesized that MasR deficiency will abolish protection of female HF-fed mice from the development of obesity-induced hypertension. Methods and Results: Female (8 weeks old, C57BL/6 background) wild type (MasR+/+) and whole body MasR deficient mice (MasR-/-) were fed a HF diet (60% Kcal as fat) for 16 weeks. MasR deficiency had no effect on the development of diet-induced obesity (MasR+/+, 45 ± 2; MasR-/-, 46 ± 2 g). In addition, MasR deficiency had no significant effect on glucose tolerance of HF-fed mice (area under the curve for blood glucose concentrations: MasR+/+, 27766 ± 1675; MasR-/-, 26275 ± 1385). At 15 weeks of HF feeding, carotid artery catheters and radiotelemetry implants were implanted into anesthetized mice, and following 1 week of recovery, blood pressure was quantified for 3-5 days. Deficiency of MasR resulted in a significant increase in diastolic blood pressure (DBP) of HF-fed females compared to controls (24hr average: MasR+/+, 88 ± 2 mmHg; MasR-/, 93 ± 2 mmHg; P<0.05). However, modest elevations in systolic blood pressure (24 hr average: MasR+/+, 125 ± 2 mmHg; MasR-/-, 128 ± 2 mmHg; p=0.38) and mean arterial pressure (24 hr average: MasR+/+, 107 ± 2 mmHg; MasR-/-, 111 ± 2 mmHg; p=0.16) of HF-fed female MasR deficient mice were not statistically significant. Conclusion: Deficiency of MasR promoted elevations in diastolic blood pressure of female obese mice. These results suggest that the ACE2/Ang-(1-7)/MasR axis contributes to protection of obese females from obesity-induced hypertension.