Endogenous Opioids and Exercise Induced Cardioprotection

Abstract

Acute exercise exposure dramatically decreases tissue injury and cellular death that results during the ischemia–reperfusion (IR) events of myocardial infarction, though the mechanisms aren’t fully understood. Existing evidence indicates endogenous opioids are a critical component of exercise-induced cardioprotection, and may be linked to the cardioprotective peptide, calcitonin gene related peptide (CGRP). The specific opioid and/or receptor subtype responsible for these effects is unknown. Based upon pharmacological research, the delta opioid receptor appears to be the most likely opioid receptor involved in cardioprotection. The purpose of this study is to determine if the delta opioid receptor is involved in opioid-mediated exercise-induced cardioprotection. Seventy three rats were randomly assigned into an unstressed (n=32) or IR group (n=41). Animals in the unstressed group performed treadmill exercise, or remained sedentary. The effect of exercise on the mRNA and protein expression of the opioid compound leu-enkephalin, and delta opioid receptor, and CGRP were determined at 0min, 20min, and 120min following exercise. Leu-enkephalin mRNA expression was significantly increased at 0min and 120min following exercise (p = 0.03 and p = 0.021, respectively). However, no significant differences were found in tissue protein content. Animals exposed to IR were randomly divided into Sham, sedentary (S) or exercise (Ex) groups. A delta-opioid receptor antagonist, Naltrindole, was administered (5 mg/kg i.p injection) 15 minutes prior to exercise in a subset of animals (ExD), and at a corresponding time in a subset of sedentary animals (SD). Twenty-four hours following the final exercise bout, animals received surgically-induced IR by left anterior descending (LAD) coronary artery ligation in vivo. Heart tissue was collected for determination of infarct area (necrotic tissue death) and apoptosis. Significant between group differences existed for tissue necrosis (p < 0.0001). Compared to Sham, S and ExD animals had significantly greater tissue necrosis (p > 0.0001, p = 0.003), while no difference existed compared to Ex groups. S had significantly increased tissue necrosis compared to Ex (p = 0.003), but was not different compared to SD. Significant between group differences existed for tissue apoptosis (p = 0.013). Compared to Sham, S had significantly greater level of apoptosis (p = 0.016), while no difference existed compared to Ex and ExD. Ex was significantly lower compared to S (p = 0.035), but not ExD. No difference existed between S and ExD or SD. These data provide evidence that the delta opioid receptor subtype is involved, at least in part, in exercise induced cardioprotection against tissue necrosis. Further research is needed to clarify the mechanisms involved in this observed protection.