Chronic ethanol-induced myocardial protection requires activation of mitochondrial K(ATP) channels.
Moderate alcohol consumption protects against coronary heart disease by unclear mechanisms. We tested whether chronic ethanol preconditioning requires activation of mitochondrial K(ATP)channels. Rats were fed 18% (v/v) ethanol in drinking water for 10 months. Blood alcohol levels at sacrifice were 3 mmol/l (0.015 gram percent). Isolated crystalloid-perfused hearts were subjected to global ischemia and reperfusion on a modified Langendorff apparatus. Prior alcohol exposure doubled the recovery of LVDP during reperfusion (45+/-5%v 20+/-3% of baseline for controls, n=6, P<0.01) and blunted the rise in LVEDP (3.5+/-0.5 v 5.5+/-0.4 times baseline for controls, n=6, P<0.01). Ethanol feeding also reduced creatine kinase release during reperfusion. Inhibition of mitochondrial K(ATP)channels with 5-hydroxydecanoate had no effect on baseline LVDP, LVEDP, or coronary flow but abolished the beneficial effects of alcohol on LV contractile recovery and myocyte necrosis. We conclude that mitochondrial K(ATP)channel activity is required for chronic ethanol-induced protection.
Zhu
P
P
Cardiology Section, University of California, San Francisco, CA, USA.
Zhou
H Z
HZ
Gray
M O
MO
D000428:Alcohol Drinking; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D003402:Creatine Kinase / Q000032:analysis; D003652:Decanoic Acids / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D006880:Hydroxy Acids / Q000494:pharmacology; D017136:Ion Transport; D019194:Ischemic Preconditioning; D007527:Isoenzymes / Q000032:analysis; D008929:Mitochondria, Heart / Q000378:metabolism*; D009124:Muscle Proteins / Q000502:physiology*; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009336:Necrosis; D011188:Potassium / Q000502:physiology*; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016277:Ventricular Function, Left / Q000187:drug effects
D003652:Decanoic Acids; D006880:Hydroxy Acids; D007527:Isoenzymes; D009124:Muscle Proteins; D015221:Potassium Channels; D000431:Ethanol; C052853:5-hydroxydecanoic acid; D003402:Creatine Kinase; D011188:Potassium