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

Eric W Dickson; Christopher P Hogrefe; Paula S Ludwig; Laynez W Ackermann; Lynn L Stoll; Gerene M Denning

doi:10.1152/ajpheart.00280.2007

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

Journal article

Peer reviewed

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

Eric W Dickson, Christopher P Hogrefe, Paula S Ludwig, Laynez W Ackermann, Lynn L Stoll and Gerene M Denning

American journal of physiology. Heart and circulatory physiology, Vol.294(1), pp.H402-408

01/2008

DOI: 10.1152/ajpheart.00280.2007

PMID: 17951371

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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.

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

Rats

Rats, Sprague-Dawley

Receptors, Opioid - genetics

Receptors, Opioid - metabolism

RNA, Messenger - metabolism

Time Factors

Details

Title: Subtitle: Exercise enhances myocardial ischemic tolerance via an opioid receptor-dependent mechanism
Creators: Eric W Dickson - University of Iowa Hospitals and Clinics
Christopher P Hogrefe - University of Iowa
Paula S Ludwig - University of Iowa
Laynez W Ackermann - University of Iowa
Lynn L Stoll - University of Iowa
Gerene M Denning - University of Iowa
Resource Type: Journal article
Publication Details: American journal of physiology. Heart and circulatory physiology, Vol.294(1), pp.H402-408
DOI: 10.1152/ajpheart.00280.2007
PMID: 17951371
ISSN: 0363-6135
eISSN: 1522-1539
Language: English
Date published: 01/2008
Academic Unit: Emergency Medicine
Record Identifier: 9984297146502771

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51 Times Cited - Web of Science