Chronic Angiotensin‐(1‐7) Treatment Prevents Obesity Hypertension in Mice

Abstract

Obesity is associated with overactivation of the renin‐angiotensin system hormone angiotensin (Ang) II, which increases blood pressure via multiple mechanisms. Conversely, Ang‐(1‐7), a vasodilatory hormone that opposes the actions of Ang II, is deficient in animal models of obesity. Our previous data show that in obese mice chronic systemic Ang‐(1‐7) administration can attenuate weight gain by increasing energy expenditure as well as improve insulin sensitivity. In this study, we hypothesized that Ang‐(1‐7) would prevent the hypertension and increased sympathetic tone also associated with this mouse model of obesity. To test this, adult male C57BL/6J mice received 12‐week Ang‐(1‐7) (400 ng/kg/min) or saline infusion via subcutaneous osmotic mini‐pumps. Immediately following mini‐pump implantation, mice were placed on a 60% high fat diet (HFD) or a standard chow diet. The three groups of mice in this study were chow diet saline (chow; n=6), HFD saline (HFD; n=3) and HFD Ang‐(1‐7) [n=8]. Blood pressure was measured during the last week of treatment via a carotid artery catheter connected to a strain‐gauge transducer and blood pressure analyzer. Cardiac sympathetic and parasympathetic tone and sympathovagal balance were calculated from the blood pressure signal using spectral analysis frequency domain methods. Consistent with our previous studies, Ang‐(1‐7) attenuated weight gain in HFD mice (36±2 chow vs. 44±2, HFD vs. 38±1 grams HFD Ang‐(1‐7); P=0.013). Ang‐(1‐7) also prevented the rise in systolic blood pressure with HFD (105±6 chow vs. 134±9 HFD vs. 111±5 mm Hg HFD Ang‐(1‐7); P=0.031), with a similar trend for diastolic blood pressure (P=0.084). There was no significant effect of Ang‐(1‐7) on heart rate (P=0.973). The Ang‐(1‐7)‐mediated blood pressure lowering in HFD mice was not associated with significant changes in cardiac sympathetic tone (P=0.303), parasympathetic tone (P=0.115), or sympathovagal balance (P=0.521). These data suggest that Ang‐(1‐7) prevents obesity hypertension in mice perhaps through autonomic‐independent mechanisms. Overall, these findings provide rationale for targeting Ang‐(1‐7) for treatment of obesity‐related hypertension.Support or Funding InformationHL122507This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.