Ma L, Robinson C P, Thadani U, Patterson E
Department of Medicine, College of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City 73190, U.S.A.
J Cardiovasc Pharmacol. 1997 Jul;30(1):130-5. doi: 10.1097/00005344-199707000-00019.
Short-term estrogen administration has been independently proposed to produce arterial vasodilation by both an indirect mechanism and a direct mechanism (inhibition of calcium entry though the L-type calcium channel). The proposed contributions of such diverse mechanisms to the vascular actions of 17beta-estradiol were examined in perfused hearts and in aortic ring sections isolated from female rabbits. In isolated rabbit hearts retrogradely perfused with Tyrode's solution, concentration-response curves to 17beta-estradiol (10(-9)-10(-5) M) were performed under control conditions and during perfusion with Bay K8644 (10(-7) M). 17beta-Estradiol produced a concentration-dependent decrease in coronary vascular resistance proportional to nitric oxide (NO) release in the presence and absence of Bay K8644. The addition of N(G)-nitro-L-arginine methyl ester (L-NAME; 10(-4) M) to the perfusate (a) completely inhibited NO formation, (b) produced a 2.3-fold and 1.55-fold rightward shift in the concentration-response curve to 17beta-estradiol for Bay K8644 treated and control hearts, respectively, and (c) failed to prevent coronary artery vasodilation. In isolated aortic rings contracted with Bay K8644, 17beta-estradiol (10(-5) M) relaxed both intact (58%) and denuded (54%) aortic rings. L-NAME (10(-4) M) completely blocked NO release in intact rings but did not prevent relaxation in denuded aortic rings. The data demonstrate (a) an endothelium-dependent relaxation by 17beta-estradiol, coincident with NO formation and suppressed by L-NAME, and (b) a direct relaxation of aortic and coronary smooth muscle independent of NO formation at higher 17beta-estradiol concentrations.
短期给予雌激素已被独立提出可通过间接机制和直接机制（抑制钙通过L型钙通道进入）产生动脉血管舒张。在灌注心脏和从雌性兔分离的主动脉环切片中研究了这些不同机制对17β-雌二醇血管作用的贡献。在逆行用Tyrode溶液灌注的离体兔心脏中，在对照条件下以及在用Bay K8644（10(-7)M）灌注期间，进行了对17β-雌二醇（10(-9)-10(-5)M）的浓度-反应曲线实验。在存在和不存在Bay K8644的情况下，17β-雌二醇使冠状动脉血管阻力呈浓度依赖性降低，与一氧化氮（NO）释放成比例。向灌注液中添加N(G)-硝基-L-精氨酸甲酯（L-NAME；10(-4)M）：（a）完全抑制NO形成；（b）使Bay K8644处理的心脏和对照心脏对17β-雌二醇的浓度-反应曲线分别向右移动2.3倍和1.55倍；（c）未能阻止冠状动脉血管舒张。在与Bay K8644收缩的离体主动脉环中，17β-雌二醇（10(-5)M）使完整（58%）和去内皮（54%）的主动脉环舒张。L-NAME（10(-4)M）完全阻断完整环中的NO释放，但不能阻止去内皮主动脉环的舒张。数据表明：（a）17β-雌二醇引起的内皮依赖性舒张，与NO形成同时发生并被L-NAME抑制；（b）在较高17β-雌二醇浓度下，主动脉和冠状动脉平滑肌的直接舒张独立于NO形成。
