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

Am J Physiol Heart Circ Physiol. 2008 Jan;294(1):H402-8. doi: 10.1152/ajpheart.00280.2007. Epub 2007 Oct 19.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Disease Models, Animal
  • 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*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Opioid / genetics
  • Receptors, Opioid / metabolism*
  • Time Factors

Substances

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