Myocardial contractile dysfunction induced by ovariectomy requires AT1 receptor activation in female rats

Estrogen deficiency induces myocardial contractile dysfunction and increases cardiovascular disease risk. However, the mechanism underlying this response is unclear. Our aim was to investigate whether AT(1)receptor blockade would prevent ovariectomy-induced myocardial contractile dysfunction.

Female rats (8 weeks old, 280 g) that underwent bilateral ovariectomy were randomly assigned to receive daily treatment with losartan (OVX + LOS, 15 mg/kg, s.c., in 0.9 % NaCl), placebo (OVX), estrogen replacement (OVX + E2, 1 mg/ kg, once a week, i.m.) and SHAM for 58 days.

Losartan and estrogen treatment 1) prevented ovariectomy-induced weight gain and slight hypertrophy, 2) restored the positive inotropic responses to Ca(2+) and isoproterenol in the isolated papillary muscle in the OVX group, 3) prevented the reduction in SERCA2a levels and the increase in phospholamban (PLB) expression in the OVX group, 4) abolished the increase in superoxide anion that was increased in the OVX group, and 5) normalized the increase in p22(phox) expression after ovariectomy. Estrogen treatment but not losartan restored the increase in serum angiotensin converting enzyme activity in the OVX group.

This study demonstrated that myocardial contractile dysfunction induced by ovariectomy and expression of key Ca(2+)-handling proteins were prevented by losartan treatment and that AT(1) receptor activation is involved in this response.