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

Abstract

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.

• Authors: Eric W Dickson, Christopher P Hogrefe, Paula S Ludwig, Laynez W Ackermann, Lynn L Stoll, Gerene M Denning
• Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 294 Issue 1 Pg. H402-8 (Jan 2008) ISSN: 0363-6135 [Print] United States
• PMID: 17951371 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Narcotic Antagonists
• Opioid Peptides
• Protein Precursors
• RNA, Messenger
• Receptors, Opioid
• Naltrexone

Topics

• Animals
• Apoptosis (genetics)
• Disease Models, Animal
• Gene Expression
• Inflammation (genetics, metabolism)
• Male
• Myocardial Ischemia (complications, genetics, metabolism, pathology, prevention & control)
• Myocardial Reperfusion Injury (etiology, genetics, metabolism, pathology, prevention & control)
• Myocardium (metabolism, pathology)
• Naltrexone (pharmacology)
• Narcotic Antagonists (pharmacology)
• Opioid Peptides (genetics, metabolism)
• Physical Exertion
• Protein Precursors (genetics, metabolism)
• RNA, Messenger (metabolism)
• Rats
• Rats, Sprague-Dawley
• Receptors, Opioid (genetics, metabolism)
• Time Factors