Exercise enhances myocardial ischemic tolerance via an opioid receptor-dependent mechanism

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 294; no. 1; pp. H402 - H408
• Main Authors: Dickson, Eric W, Hogrefe, Christopher P, Ludwig, Paula S, Ackermann, Laynez W, Stoll, Lynn L, Denning, Gerene M
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.01.2008
• Subjects: Animals; Apoptosis - genetics; Cardiovascular system; Disease Models, Animal; Exercise; Gene Expression; Inflammation - genetics; Inflammation - metabolism; Male; Myocardial Ischemia - complications; Myocardial Ischemia - genetics; Myocardial Ischemia - metabolism; Myocardial Ischemia - pathology; Myocardial Ischemia - prevention & control; Myocardial Reperfusion Injury - etiology; Myocardial Reperfusion Injury - genetics; Myocardial Reperfusion Injury - metabolism; Myocardial Reperfusion Injury - pathology; Myocardial Reperfusion Injury - prevention & control; Myocardium - metabolism; Myocardium - pathology; Naltrexone - pharmacology; Narcotic Antagonists - pharmacology; Opioid Peptides - genetics; Opioid Peptides - metabolism; Physical Exertion; Protein Precursors - genetics; Protein Precursors - metabolism; Proteins; Rats; Rats, Sprague-Dawley; Receptors, Opioid - genetics; Receptors, Opioid - metabolism; RNA, Messenger - metabolism; Rodents; Time Factors
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00280.2007

Department of Emergency Medicine, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa Submitted 6 March 2007 ; accepted in final form 15 October 2007 Exercise increases serum opioid levels and improves cardiovascular health. Here we tested the hypothesis that opioids contribute to the acute cardioprotective effects of exercise using a rat model of exercise-induced cardioprotection. For the standard protocol, rats were randomized to 4 days of treadmill training and 1 day of vigorous exercise ( day 5 ), or to a sham exercise control group. On day 6 , animals were killed, and global myocardial ischemic tolerance was assessed on a modified Langendorff apparatus. Twenty minutes of ischemia followed by 3 h of reperfusion resulted in a mean infarct size of 42 ± 4% in hearts from sham exercise controls and 21 ± 3% ( P < 0.001) in the exercised group. The cardioprotective effects of exercise were gone by 5 days after the final exercise period. To determine the role of opioid receptors in exercise-induced cardioprotection, rats were exercised according to the standard protocol; however, just before exercise on days 4 and 5 , rats were injected subcutaneously with 10 mg/kg of the opioid receptor antagonist naltrexone. Similar injections were performed in the sham exercise control group. Naltrexone had no significant effect on baseline myocardial ischemic tolerance in controls (infarct size 43 ± 4%). In contrast, naltrexone treatment completely blocked the cardioprotective effect of exercise (infarct size 40 ± 5%). Exercise was also associated with an early increase in myocardial mRNA levels for several opioid system genes and with sustained changes in a number of genes that regulate inflammation and apoptosis. These findings demonstrate that the acute cardioprotective effects of exercise are mediated, at least in part, through opioid receptor-dependent mechanisms that may include changes in gene expression. exercise; myocardial ischemic tolerance; enkephalins; opioid receptors Address for reprint requests and other correspondence: E. W. Dickson, Dept. of Emergency Medicine, Univ. of Iowa Hospitals and Clinics, 200 Hawkins Dr., 1193 RCP, Iowa City, Iowa, 52242-1009 (e-mail: eric-dickson{at}uiowa.edu )