Ischemic preconditioning and morphine-induced cardioprotection involve the delta (delta) opioid receptor in the intact rat heart

Several investigators have demonstrated that the opioid pathway is involved in tissue preservation during hypoxia or ischemia and that this protection is mediated via the delta (delta)-opioid receptor. Subsequently we have shown that opioid receptors are involved in ischemic preconditioning (PC) in the rat heart and that morphine produces a cardioprotective effect; however, the class of opioid receptors involved in mediating these effects is still unknown. Therefore, the purpose of the present study was to test the hypothesis that ischemia- and morphine-induced cardioprotection are mediated via stimulation of the delta-opioid receptor in the rat heart, Anesthetized, open-chest Wistar rats were subjected to one of six protocols, The control group was subjected to 30 min of occlusion and 2 h of reperfusion. Ischemic PC was elicited by three 5 min occlusion periods interspersed with 5 min of reperfusion, Morphine-induced cardioprotection was produced by three 5 min morphine infusions (100 mu g/kg/infusion. i.v.) interspersed with a 5-min drug-free period. To determine if the delta-opioid receptor has a role in ischemic PC and morphine-induced cardioprotection, naltrindole (NTI), a selective delta-opioid receptor antagonist, was utilized. NTI (5 mg/kg, i.v.) was given 10 min prior to ischemic PC (NTI+PC) or morphine infusion (NTI+MOR). Also, NTI (5 mg/kg, i.v.) was given 10 min before the 30 min occlusion period in untreated rats. Infarct size (IS) as a percent of the area at risk (AAR) was determined by 2,3,5-triphenyltetrazolium chloride staining. Ischemic PC and morphine infusions resulted in similar reductions in IS/AAR from 51+/-4 to 11+/-3 and 15+/-4%, (*P<0.05), respectively. NTI completely abolished the cardioprotective effect induced by ischemia and morphine, The results of the present study suggests a role of delta-opioid receptors in ischemic PC or morphine-induced myocardial protection in the rat. (C) 1997 Academic Press Limited.