Angiotensin‐(1‐7) Attenuates Blood Pressure and Cardiac Hypertrophy in Aged Mice

Abstract

BackgroundAging is associated with an increase in blood pressure, which is attributed to multiple factors including endothelial dysfunction, cardiac hypertrophy, and changes in cardiovascular autonomic regulation including increased sympathetic tone and reduced measures of parasympathetic tone. In addition, altered responsiveness of the renin‐angiotensin hormone angiotensin (Ang) II has been implicated in age‐related cardiovascular risk. The deleterious actions of Ang II are generally opposed by the vasodilatory and cardioprotective hormone Ang‐(1‐7); however, to our knowledge no studies have evaluated the importance of Ang‐(1‐7) to blood pressure regulation during aging. In this study, we hypothesized that Ang‐(1‐7) would improve blood pressure and cardiac autonomic control in healthy aged mice.MethodsSixteen month‐old male C57BL/6J mice received 6‐week Ang‐(1‐7) [400 ng/kg/min, n=5] or saline infusion (n=3) via subcutaneous osmotic mini‐pumps. All mice were fed standard chow diet (18% kcal from fat). 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. Heart weight and the heart: body weight ratio was determined at end of experiments.ResultsAng‐(1‐7) significantly decreased systolic [Ang‐(1‐7): 102±1 mmHg, saline: 112±6 mmHg, P=0.050] diastolic [Ang‐(1‐7): 78±2 mmHg, saline: 85±2 mmHg, P=0.033], and mean [Ang‐(1‐7): 86±2 mmHg, 94±3 mmHg, P=0.029] blood pressure in aged mice. The blood pressure‐lowering effect of Ang‐(1‐7) was associated with a trend towards reduced sympathetic tone [Ang‐(1‐7): 0.17±0.06, saline: 0.29±0.03, P=0.081], with no effect on vagal tone [Ang‐(1‐7): 0.25±0.11, saline: 0.17±0.06, P=0.625]. Furthermore, Ang‐(1‐7) reduced heart weight [Ang‐(1‐7): 0.19±0.01 g; saline: 0.23±0.02 g, P=0.044] and the heart to body weight ratio [Ang‐(1‐7): 0.004±0.001; saline: 0.006±0.001, P=0.022]. There was no effect of Ang‐(1‐7) on body weight or composition (P > 0.2).ConclusionsChronic Ang‐(1‐7) treatment lowers blood pressure and attenuates cardiac hypertrophy in aged mice, even in the absence of effects on body composition. The blood pressure‐lowering effects of Ang‐(1‐7) appear to involve a decrease in cardiac sympathetic tone; although further studies are needed to confirm these findings. These overall data suggest Ang‐(1‐7) may provide a novel pharmacological target to improve age‐related cardiovascular risk.Support or Funding InformationNIH 5 R00 HL122507‐04, American Heart Association Postdoctoral Fellowship 18POST33960087This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.