Sustained exogenous administration of Met5-enkephalin protects against infarction in vivo.
The opioid antagonist naloxone abolishes infarct limitation by myocardial ischemic preconditioning, suggesting that one or more endogenous opioid peptides can mediate cardiac protection against ischemic damage. We tested the hypothesis that the naturally occurring opioid peptide Met5-enkephalin (ME) modulates myocardial infarct size in vivo. Experiments were conducted in barbiturate-anesthetized open-chest rabbits subjected to regional myocardial ischemia-reperfusion. ME was administered via osmotic minipump for 24 h. Infarct size was assessed with tetrazolium and is expressed as a percentage of the area at risk. Exogenous ME reduced the amount of the risk zone infarcted by approximately 60% compared with saline-treated controls. ME-induced protection was sensitive to opioid receptor blockade with naloxone [NAL 50 +/- 2% vs. ME + NAL 39 +/- 3%, P = not significant (NS)] and also to blockade of sarcolemmal and mitochondrial ATP-sensitive K+ (KATP) channels [5-hydroxydecanoate (5-HD) 33 +/- 3% vs. ME + 5-HD 43 +/- 8%, P = NS; and HMR-1098 60 +/- 3% vs. ME + HMR-1098 54 +/- 7%, P = NS]. We conclude that ME limits ischemic injury in vivo by an opioid receptor-mediated mechanism that involves both sarcolemmal and mitochondrial KATP channels.
Kuzume
Koh
K
Department of Anesthesiology, Oregon Health and Sciences University, Portland, 97201, USA.
Wolff
Roger A
RA
Amakawa
Kazuhiko
K
Kuzume
Kazuyo
K
Van Winkle
Donna M
DM
D000818:Animals; D001831:Body Temperature; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003327:Coronary Disease / Q000188:drug therapy / Q000473:pathology; D004744:Enkephalin, Methionine / Q000494:pharmacology*; D006339:Heart Rate; D019194:Ischemic Preconditioning; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D015221:Potassium Channels / Q000378:metabolism; D011817:Rabbits
D002316:Cardiotonic Agents; D015221:Potassium Channels; D004744:Enkephalin, Methionine