• T M Lee, S F Su, C C Tsai, Y T Lee, and C H Tsai.
• Department of Internal Medicine, National Taiwan University, Taipei, Taiwan.
• J. Mol. Cell. Cardiol. 2000 Jul 1; 32 (7): 1147-58.

AbstractWe have previously demonstrated the effects of estrogen on modulation of myocardial ATP-sensitive K(+)(K(ATP)) channel. Previous studies have demonstrated that activation of mitochondrial K(ATP)channel is a major contributor of ischemic cardioprotection. The purpose of the present study was to investigate the role of K(ATP)channel in estrogen-induced myocardial protection after ischemia/reperfusion in dogs. Anaesthetized dogs were subjected to 60 min of left anterior descending coronary artery occlusion followed by 2 h of reperfusion. In a first study to characterize effects of sex and the dose-response profile of estrogen on infarct size, the drug was intravenously administered at 10 or 20 microg/kg. In a second study to investigate the cardioprotective mechanisms of estrogen, vehicle, preconditioning or 17 beta -estradiol (10 microg/kg) was given, beginning 15 min prior to the 60 min occlusion period in the presence or absence of 5-hydroxydecanoate (5-HD). In the first study, administration of 17 beta -estradiol resulted in a significant, dose-dependent limitation of infarct size. Estrogen administration provided myocardial protection of similar magnitude in both males and females. In the second study, infarct size in control animals averaged 39+/-5% of the risk region, compared with 14+/-5% of the risk region in estrogen-treated dogs and 6+/-5% of the risk region in preconditioning dogs (both P<0.0001 v controls). Pretreatment with 5-HD completely abolished preconditioning- and estrogen-induced cardioprotection. Estrogen limits myocardial infarction size resulting from coronary artery occlusion and reperfusion in a dose-dependent fashion, irrespective of gender difference. The infarct size-limiting effect of estrogen++ was abolished by 5-HD, suggesting that the cardioprotective effect of estrogen may result from activation of myocardial mitochondrial K(ATP)channels.Copyright 2000 Academic Press.

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