Ma L, Yu Z, Xiao S, Thadani U, Robinson C P, Patterson E
Department of Medicine, College of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City 73190, USA.
Eur J Pharmacol. 1998 Oct 23;359(2-3):191-200. doi: 10.1016/s0014-2999(98)00644-x.
The modulating role of estrogens and ovariectomy on coronary artery and thoracic aortic rings was examined in female rabbits. Three treatment groups were studied: (1) control, (2) ovariectomy, and (3) ovariectomy + 17beta-estradiol acetate (40 microg/kg per day, i.m. for 7 days). Coronary artery reactivity was studied in the isolated retrogradely perfused heart. Aortic reactivity was studied using endothelium intact and denuded aortic rings. Concentration-response curves were performed to serotonin (5-HT) and histamine. A 21-fold, a 4.7-fold, and a 5.2-fold increase in sensitivity to 5-HT-induced contraction were observed in the ovariectomy group compared to the control group for coronary artery, intact aortic, and denuded aortic preparations, respectively (P < 0.05 for each comparison). Similarly, 34-fold, 4.9-fold, and 5.0-fold increases in sensitivity to histamine-induced contraction were observed in the ovariectomy group compared to control group for coronary artery, intact aortic, and denuded aortic preparations, respectively (P < 0.05 for each comparison). 17beta-Estradiol administration reversed the supersensitivity to serotonin- and histamine-induced vascular contraction observed following ovariectomy. No differences in EC50 or maximal contraction were noted between control and ovariectomy + estrogen groups. Baseline nitric oxide release and maximal 5-HT- and histamine-induced nitric oxide release from the perfused heart were decreased (P < 0.05) in ovariectomy rabbits compared to control and ovariectomy + estrogen treatment groups. The data demonstrate that (1) reduced autacoid-induced nitrous oxide release following ovariectomy and (2) direct effects upon the vascular smooth muscle contractility, which are probably mediated by altered receptor sensitivity by ovariectomy and estrogen replacement therapy. The information obtained from this study provides additional information regarding possible beneficial actions of estrogen replacement therapy in post-menopausal women.
在雌性兔子中研究了雌激素和卵巢切除术对冠状动脉和胸主动脉环的调节作用。研究了三个治疗组：(1) 对照组，(2) 卵巢切除组，以及 (3) 卵巢切除 + 17β - 醋酸雌二醇组（40微克/千克/天，肌肉注射，持续7天）。在离体逆行灌注心脏中研究冠状动脉反应性。使用内皮完整和去内皮的主动脉环研究主动脉反应性。绘制了对5 - 羟色胺（5 - HT）和组胺的浓度 - 反应曲线。与对照组相比，卵巢切除组在冠状动脉、完整主动脉和去内皮主动脉制剂中对5 - HT诱导收缩的敏感性分别增加了21倍、4.7倍和5.2倍（每次比较P < 0.05）。同样，与对照组相比，卵巢切除组在冠状动脉、完整主动脉和去内皮主动脉制剂中对组胺诱导收缩的敏感性分别增加了34倍、4.9倍和5.0倍（每次比较P < 0.05）。给予17β - 雌二醇可逆转卵巢切除后观察到的对5 - HT和组胺诱导的血管收缩的超敏感性。对照组和卵巢切除 + 雌激素组之间的半数有效浓度（EC50）或最大收缩无差异。与对照组和卵巢切除 + 雌激素治疗组相比，卵巢切除兔子中灌注心脏的基线一氧化氮释放以及最大5 - HT和组胺诱导的一氧化氮释放均降低（P < 0.05）。数据表明：(1) 卵巢切除后自分泌诱导的一氧化二氮释放减少；(2) 对血管平滑肌收缩力有直接影响，这可能是由卵巢切除和雌激素替代疗法改变受体敏感性介导的。从本研究中获得的信息提供了关于雌激素替代疗法在绝经后女性中可能的有益作用的更多信息。
