Role of Endogenous Opioid System in Ischemic-Induced Late Preconditioning

Background Opioid receptors (OR) are involved in myocardial late preconditioning (LPC) induced by morphine and delta 1-opioid receptor (delta 1-OR) agonists. The role of OR in ischemic-induced LPC is unknown. We investigated whether 1) OR are involved in the trigger and/or mediation phase of LPC and 2) a time course effect on the expression of different opioid receptors and their endogenous ligands exists. Methods Male Wistar rats were randomly allocated to four groups (each group n = 8). Awake animals were ischemic preconditioned by a 5 minutes coronary occlusion. 24 hours later, anesthetized animals underwent 25 minutes coronary occlusion followed by 2 hours of reperfusion. The role of OR was investigated by treatment with intraperitoneal naloxone (Nal) 10 minutes prior to LPC (Nal-LPC; trigger phase) or 10 min prior to sustained ischemia (LPC-Nal; mediation phase). Results LPC reduced infarct size from 61 +/- 10% in controls to 25 +/- 9% (P<0.001). Naloxone during trigger or mediation phase completely abolished LPC-induced cardioprotection (59 +/- 9% and 62 +/- 9%; P<0.001 vs. LPC). 8, 12 and 24 hours after the ischemic stimulus, expression of delta-OR in the heart was increased, whereas mu-opioid receptor (mu-OR) and kappa-opioid receptor (kappa-OR) were not. Plasma concentrations of beta-endorphin and leu-enkephalin but not dynorphin were increased by LPC. Conclusion Ischemic LPC is triggererd and mediated by OR. Expression of delta-OR and plasma levels of endogenous opioid peptides are increased after ischemic LPC.