title: Amelioration of ischemia- and reperfusion-induced myocardial injury by 17beta-estradiol: role of nitric oxide and calcium-activated potassium channels.
abstract: BACKGROUND
  17Beta-estradiol increases the production of nitric oxide (NO) and prostacyclin and opens Ca2+-activated K+ (K(Ca)) channels. Whether these effects of 17beta-estradiol reduce infarct size and the incidence of ventricular arrhythmia was investigated in dogs subjected to myocardial ischemia and reperfusion.
  
  
  RESULTS
  Infarct size was measured in open-chest dogs after 90 minutes' occlusion of the left anterior descending coronary artery and a subsequent 6 hours of reperfusion. Infusion of 17beta-estradiol into the coronary artery was initiated 10 minutes before coronary occlusion and continued until after 1 hour of reperfusion, with the exception of the occlusion period. The difference in NO concentration between coronary venous and arterial blood 10 minutes after the onset of reperfusion was significantly greater in dogs treated with 17beta-estradiol (10 ng x kg(-1) x min(-1)) than in control animals. Infarct size (13.1+/-3.0% versus 43.7+/-5.4% of the area at risk) and the incidence of ventricular arrhythmia during ischemia and reperfusion periods were significantly reduced in the 17beta-estradiol group. Both N(G)-nitro-L-arginine methyl ester (an inhibitor of NO synthase) and iberiotoxin (a blocker of K(Ca) channels) reduced both the infarct size-limiting effect (infarct size, 29.3+/-3.0% and 31.7+/-2.1%, respectively) and the antiarrhythmic effect of 17beta-estradiol; indomethacin (an inhibitor of cyclooxygenase) did not attenuate the beneficial effects of 17beta-estradiol.
  
  
  CONCLUSIONS
  17Beta-estradiol reduced both myocardial infarct size and the occurrence of ischemia- and reperfusion-induced ventricular arrhythmias, which appear to be mediated by NO and the opening of K(Ca) channels in canine hearts.
authors.affiliation: First Department of Medicine, Osaka University School of Medicine, Suita, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Node
authors.forename: M
authors.initials: M
authors.lastname: Kitakaze
authors.forename: H
authors.initials: H
authors.lastname: Kosaka
authors.forename: T
authors.initials: T
authors.lastname: Minamino
authors.forename: H
authors.initials: H
authors.lastname: Funaya
authors.forename: M
authors.initials: M
authors.lastname: Hori
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D006352:Heart Ventricles / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D015640:Ion Channel Gating / Q000502:physiology; D009203:Myocardial Infarction / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D017202:Myocardial Ischemia / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D017180:Tachycardia, Ventricular / Q000188:drug therapy / Q000209:etiology; D014118:Toxins, Biological / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; D010455:Peptides; D015221:Potassium Channels; D014118:Toxins, Biological; D009569:Nitric Oxide; D004958:Estradiol; C064719:iberiotoxin; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin