Patterson E, Ma L, Szabo B, Robinson C P, Thadani U
Department of Pharmacology, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
J Pharmacol Exp Ther. 1998 Feb;284(2):586-91.
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 microg/kg/day i.m. 17beta-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 17beta-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 for 3H-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.
在雌性兔中研究了卵巢切除术和雌激素替代对心肌收缩力的影响。卵巢切除术未能改变左心室质量、乳头肌横截面积或等长力。卵巢切除术后给予雌激素替代（0.15微克/千克/天，肌肉注射醋酸17β-雌二醇，共7天），与对照组和卵巢切除组相比，增加了左心室质量和乳头肌质量，并降低了等长力。卵巢切除术未改变异丙肾上腺素引起的等长力增加，但降低了Bay K8644的半数有效剂量（ED50）（与对照组和雌激素组相比）。与对照组和卵巢切除组相比，雌激素替代增加了异丙肾上腺素和Bay K8644诱导的等长力的ED50。卵巢切除术增加而雌激素替代降低了与细胞外钙离子浓度升高相关的等长力。急性暴露于17β-雌二醇或己烯雌酚（10^-7 M，10^-6 M）未能改变对照乳头肌的等长力。雌激素替代减少了质膜制剂中3H-尼群地平结合的数量，但未改变解离常数（与卵巢切除组和对照组相比）。三个治疗组分离的心室肌细胞中的L型钙电流峰值无显著差异。这些数据与卵巢切除引起的兔心肌中L型钙通道密度增加以及雌激素引起的降低一致。雌激素诱导的L型钙通道表达和收缩力的改变随后被雌激素诱导的心脏肥大所修饰。
