Chester A H, Jiang C, Borland J A, Yacoub M H, Collins P
Department of Cardiothoracic Surgery, National Heart and Lung Institute, Harefield Hospital, UK.
Coron Artery Dis. 1995 May;6(5):417-22. doi: 10.1097/00019501-199505000-00009.
Oestrogen-replacement therapy is associated with a reduced incidence of cardiovascular disease. The acute administration of oestrogen improves myocardial ischemia in women with coronary heart disease. In this study we investigated the relaxing effect of oestradiol-17 beta on human coronary arteries in vitro and determined the role of endothelial modulation in this relaxation by using isolated human coronary arteries.
Atherosclerosis-free epicardial arteries from men and women were removed from patients undergoing heart or combined heart and lung transplantation. The arteries were cut into ring segments and placed into organ baths containing Tyrode's solution. Changes in isometric tension were measured. The relaxing response to oestradiol-17 beta (10(-10) - 10(-5) mol/l) was investigated and the effects of endothelium, NGmonomethyl-L-arginine and indomethacin on the response of oestradiol-17 beta were assessed.
Oestradiol-17 beta (10(-10) - 10(-5) mol/l) induced significant relaxation in coronary arteries pre-contracted with the thromboxane A2 analog (U46619; 3 x 10(-8) mol/l). Relaxation was significantly greater in coronary arteries from female patients. No significant differences were observed between arteries with or without endothelium nor after nitric oxide synthase or cyclo-oxygenase inhibition. These results indicate that oestradiol-17 beta induces human coronary artery relaxation via an endothelium-independent mechanism in vitro. The sex of the patients significantly affects sensitivity of the coronary arterial rings to oestrogen.
Oestradiol-17 beta-induced coronary relaxation may play an important role in regulation of coronary tone, and may partly explain why oestrogen improves myocardial ischemia in women and why it protects postmenopausal women from the risk of developing coronary heart disease.
雌激素替代疗法与心血管疾病发病率降低相关。急性给予雌激素可改善冠心病女性的心肌缺血。在本研究中，我们在体外研究了17β-雌二醇对人冠状动脉的舒张作用，并通过使用离体人冠状动脉确定了内皮调节在这种舒张中的作用。
从接受心脏或心肺联合移植的患者中取出无动脉粥样硬化的男女心外膜动脉。将动脉切成环状节段，放入含有台氏液的器官浴中。测量等长张力的变化。研究了对17β-雌二醇（10⁻¹⁰ - 10⁻⁵mol/L）的舒张反应，并评估了内皮、N-单甲基-L-精氨酸和吲哚美辛对17β-雌二醇反应的影响。
17β-雌二醇（10⁻¹⁰ - 10⁻⁵mol/L）可使预先用血栓素A2类似物（U46619；3×10⁻⁸mol/L）预收缩的冠状动脉产生显著舒张。女性患者冠状动脉的舒张作用明显更强。有或无内皮的动脉之间以及一氧化氮合酶或环氧化酶抑制后均未观察到显著差异。这些结果表明，17β-雌二醇在体外通过非内皮依赖机制诱导人冠状动脉舒张。患者的性别显著影响冠状动脉环对雌激素的敏感性。
17β-雌二醇诱导的冠状动脉舒张可能在冠状动脉张力调节中起重要作用，并且可能部分解释了为什么雌激素可改善女性的心肌缺血以及为什么它可保护绝经后女性免受患冠心病风险的影响。
