Moderate chronic aortic constriction induces modest, sex-specific effects on rat hearts and skeletal muscle

Abstract

Heart failure with preserved ejection fraction (HFpEF) accounts for ∼50 % of heart failure diagnoses, occurs in older individuals, is more prevalent in females than males, and includes hypertension as contributing factor. We sought to determine whether a long-term, moderate, transverse aortic constriction in male and female rats induces ventricular hypertrophy and preserved ejection fraction, changes in skeletal muscle mass and strength, and sex-specific differences in these outcomes, mimicking HFpEF. Transverse aortic constriction (TAC) surgery was performed on male and female rats at 4 weeks of age, and rats were sacrificed 40 weeks after surgery, following echocardiography and grip strength measures. Male TAC rats demonstrated a 12 % greater heart mass and 17 % higher heart to body mass ratio than Sham rats; however, these parameters did not differ between female TAC and Sham rats. TAC rats demonstrated a preserved ejection fraction, and TAC had no effect on skeletal muscle size or strength. In summary, male rats were more susceptible to TAC-induced pressure-overload hypertrophy than female rats, and this moderate constriction resulted in preserved ejection fraction despite a long time course. Collectively, these investigations reveal, in the absence of comorbidities, pressure overload produces modest, sex-specific effects in the myocardium and skeletal muscle.