Influence of ACE inhibitors on frailty, cardiac contractile function and calcium homeostasis in middle-aged male and female mice
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Angiotensin Converting Enzyme (ACE) inhibitors were chronically administered to middle-aged male and female mice to determine whether treatment with ACE inhibitors attenuates frailty and whether this is accompanied by changes in cardiac function. In females, enalapril-treated mice had lower frailty scores compared to controls after 3 mos. Frailty scores were not different between male ACE inhibitor-treated and control groups after treatment. Echocardiography showed no changes in in vivo cardiac structure or function between enalapril-treated and control animals of both sexes. Individual ventricular myocytes showed improved contractile function in enalapril-treated females compared to controls. Interestingly, this was not associated with changes in intracellular Ca2+ handling. Males showed no difference in contractile function or Ca2+ handling between enalapril-treated and control mice. Males had improved contractile function and Ca2+ handling compared to females. These results suggest that enalapril-treatment may attenuate frailty in females, at least in part, by improving myocyte contractile function.