Abstract

The effects of ovariectomy and estrogen replacement on myocardial contractility were examined in female rabbits. Ovariectomy failed to alter left ventricular mass, papillary muscle cross-sectional area or isometric force. Estrogen replacement after ovariectomy (0.15 μg/kg/day i.m. 17β-estradiol acetate for 7 days) increased left ventricular mass and papillary muscle mass, and reduced isometric force compared to control and ovariectomy groups. Ovariectomy did not alter increased isometric force with isoproterenol, but decreased the ED₅₀ for Bay K8644 (compared to control and estrogen groups). Estrogen replacement increased the ED₅₀ for isoproterenol- and Bay K8644-induced isometric force compared to control and ovariectomy groups. Ovariectomy increased and estrogen replacement decreased isometric force associated with increased Ca^++_o. Acute exposure to 17β-estradiol or diethylstilbesterol (10⁻⁷ M, 10⁻⁶ M) failed to alter isometric force in control papillary muscles. Estrogen replacement reduced the number, but not the dissociation constant for³H-nitrendipine binding in plasma membrane preparations (compared to ovariectomy and control groups). Peak L-type calcium currents in isolated ventricular myocytes from the three treatment groups were not significantly different. The data are consistent with an ovariectomy-induced increase and estrogen-induced decrease in L-type calcium channel density in rabbit myocardium. Estrogen-induced alterations in L-type calcium channel expression and contractility are subsequently modified by estrogen-induced cardiac hypertrophy.