ANGIOTENSIN II-INDUCED HEART FAILURE DIFFERS BETWEEN THE SEXES AND EXACERBATES FRAILTY IN A SEX SPECIFIC FASHION IN OLDER C57BL/6 MICE

Abstract

This study investigated sex differences in cardiac remodeling in an angiotensin II (Ang II) infused mouse model of heart failure (HF) in older C57BL/6 mice and whether HF exacerbates frailty in a sex-specific fashion. Male and female mice were infused with either Ang II to increase blood pressure or saline (6 weeks). Echocardiography showed concentric hypertrophy with slight left ventricular (LV) chamber dilation in treated females and eccentric hypertrophy with marked LV chamber dilation in males. Treated males had more pronounced diastolic and systolic dysfunction than females. Contractile function was reduced in Langendorff-perfused hearts from treated males but not females. Ang II-treated females exhibited worse cardiac hypertrophy and pulmonary edema. Treated mice had high frailty, increased biological age and lower life expectancies, but this was more pronounced in males. These findings suggest that Ang II-induced hypertension promoted HF in a sex-specific fashion, and these effects were especially severe in males.