Angiotensin-(1-7) Improves Integrated Cardiometabolic Function in Aged Mice

Abstract

Angiotensin (Ang)-(1-7) is a beneficial renin–angiotensin system (RAS) hormone that elicits protective cardiometabolic effects in young animal models of hypertension, obesity, and metabolic syndrome. The impact of Ang-(1-7) on cardiovascular and metabolic outcomes during aging, however, remains unexplored. This study tested the hypothesis that Ang-(1-7) attenuates age-related elevations in blood pressure and insulin resistance in mice. Young adult (two-month-old) and aged (16-month-old) male C57BL/6J mice received Ang-(1-7) (400 ng/kg/min) or saline for six-weeks via a subcutaneous osmotic mini-pump. Arterial blood pressure and metabolic function indices (body composition, insulin sensitivity, and glucose tolerance) were measured at the end of treatment. Adipose and cardiac tissue masses and cardiac RAS, sympathetic and inflammatory marker gene expression were also measured. We found that chronic Ang-(1-7) treatment decreased systolic and mean blood pressure, with a similar trend for diastolic blood pressure. Ang-(1-7) also improved insulin sensitivity in aged mice to levels in young mice, without effects on glucose tolerance or body composition. The blood pressure–lowering effects of Ang-(1-7) in aged mice were associated with reduced sympathetic outflow to the heart. These findings suggest Ang-(1-7) may provide a novel pharmacological target to improve age-related cardiometabolic risk.

Novel Proteome Targets Marking Insulin Resistance in Metabolic Syndrome

“…Interestingly, obese ACE2-deficient mice have increased myocardial insulin resistance, which also increases oxidative stress [ 50 ]. Furthermore, angiotensin 1-7 administration in wild-type mice improved insulin sensitivity without effects on body composition or glucose tolerance [ 51 ]. In our study, ACE2 was associated with high glucose concentrations consistently throughout the cohort in subjects with MetSyn but not in obese subjects without MetSyn, suggesting that obesity and therefore increased adipose tissue alone is not sufficient for ACE2 induction, but that MetSyn perturbations are necessary, or perhaps that a prolonged exposure to increased adipose tissue might increase circulating ACE2.…”

Novel Insights into the Cardioprotective Effects of the Peptides of the Counter-Regulatory Renin–Angiotensin System

“…This research was conducted in order to test the idea that IL-10 has an immunomodulatory effect on the vasculature and that Ang(1-7) also has modulatory effects that are advantageous in many tissues. However, given that most of the research focuses on demonstrating the preventive cardiometabolic benefits in young animals, it is interesting to highlight a study conducted in 2020 that sought to evaluate the actions of Ang-(1-7) affecting the circulatory system in aged animals [64]. Infusion of Ang-(1-7) improved the cardiometabolic function, specifically systolic blood pressure, mean blood pressure, and insulin sensitivity [64].…”

“…However, given that most of the research focuses on demonstrating the preventive cardiometabolic benefits in young animals, it is interesting to highlight a study conducted in 2020 that sought to evaluate the actions of Ang-(1-7) affecting the circulatory system in aged animals [64]. Infusion of Ang-(1-7) improved the cardiometabolic function, specifically systolic blood pressure, mean blood pressure, and insulin sensitivity [64]. These lowering effects were associated with reduced measures of the cardiac sympathetic tone.…”