Cardioprotective effects of 17 beta-estradiol produced by activation ofmitochondrial ATP-sensitive K(+)Channels in canine hearts.
We 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.
Lee
T M
TM
Department of Internal Medicine, National Taiwan University, Taipei, Taiwan.
Su
S F
SF
Tsai
C C
CC
Lee
Y T
YT
Tsai
C H
CH
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001783:Blood Flow Velocity; D003652:Decanoic Acids / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006439:Hemodynamics; D006880:Hydroxy Acids / Q000494:pharmacology; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009203:Myocardial Infarction / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009336:Necrosis; D015221:Potassium Channels / Q000187:drug effects*; D015427:Reperfusion Injury; D012737:Sex Factors; D013997:Time Factors
D000889:Anti-Arrhythmia Agents; D003652:Decanoic Acids; D006880:Hydroxy Acids; D015221:Potassium Channels; D004958:Estradiol; C052853:5-hydroxydecanoic acid; D000255:Adenosine Triphosphate