title: Ischemic preconditioning and morphine-induced cardioprotection involve the delta (delta)-opioid receptor in the intact rat heart.
abstract: 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 microg/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.
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Schultz
authors.forename: A K
authors.initials: AK
authors.lastname: Hsu
authors.forename: G J
authors.initials: GJ
authors.lastname: Gross
mesh_terms: D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology* / Q000627:therapeutic use; D006321:Heart / Q000187:drug effects*; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009020:Morphine / Q000494:pharmacology* / Q000627:therapeutic use; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control; D009206:Myocardium / Q000378:metabolism*; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017465:Receptors, Opioid, delta / Q000187:drug effects / Q000502:physiology*; D013874:Thiopental / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D002317:Cardiovascular Agents; D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; C004316:thiobutabarbital; D009271:Naltrexone; D009020:Morphine; C055382:naltrindole; D013874:Thiopental