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

• Published in: International journal of molecular sciences 2020-07, Vol.21 (14), p.5131
• Main Authors: Miller, Amanda J, Bingaman, Sarah S, Mehay, Darren, Medina, Daniela, Arnold, Amy C
• Format: Article
• Language: English
• Subjects: Age; Aging; Aging - drug effects; Angiotensin; Angiotensin I - administration & dosage; Angiotensin I - pharmacology; Animal models; Animals; Antihypertensive Agents - administration & dosage; Antihypertensive Agents - pharmacology; Blood pressure; Blood Pressure - drug effects; Body composition; Cardiovascular disease; Coronary vessels; Cytokines; Diabetes; Enzymes; Gene expression; Glucose; Glucose - metabolism; Glucose tolerance; Heart; Heart rate; Hypertension; Hypertension - drug therapy; Hypertension - etiology; Hypertension - metabolism; Inflammation; Insulin; Insulin - metabolism; Insulin Resistance; Male; Metabolic disorders; Metabolic syndrome; Metabolism; Mice, Inbred C57BL; Obesity; Peptide Fragments - administration & dosage; Peptide Fragments - pharmacology; Pressure effects; Renin; Renin-Angiotensin System - drug effects; Sensitivity; Young adults
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21145131

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.