ROLES OF NO AND CA2-ACTIVATED K+ CHANNELS IN CORONARY VASODILATION INDUCED BY 17-BETA-ESTRADIOL IN ISCHEMIC HEART-FAILURE()

Estrogen induces the generation of nitric oxide (NO) and produces coro nary vasodilation by opening the Ca2+-activated K+ (K-Ca) channels, Th e hypothesis that 17 beta-estradiol produces NO and activates K-Ca cha nnels during coronary hypoperfusion was investigated, In open-chest do gs, the left anterior descending coronary artery was perfused through an extracorporeal bypass tube from the left carotid artery, 17 beta-Es tradiol was infused into the bypass tube for 20 min after coronary blo od flow was reduced by partial occlusion of the bypass tube, 17 beta-E stradiol increased the difference in NO concentrations between the cor onary venous and arterial blood as well as coronary blood flow, The la ctate extraction ratio and pH of coronary venous blood were both also increased by 17 beta-estradiol, indicating a reduction in myocardial a naerobic metabolism, Whereas the increase in the coronary arteriovenou s difference in NO concentration was completely attenuated by N-G-nitr o-L-arginine methyl ester (L-NAME, an inhibitor of NO synthase), the i ncrease in coronary blood flow induced by 17 beta-estradiol was only p artially attenuated by L-NAME. The combination of L-NAME and iberiotox in (a blocker of high-conductance K-Ca channels) completely abolished the coronary vasodilatory effect of 17 beta-estradiol, The data indica te that during coronary hypoperfusion in canine hearts, 17 beta-estrad iol increases coronary blood flow and improves metabolic dysfunction b y increasing NO release and opening K-Ca channels.