Myocardial Apoptosis and Infarction after Ischemia/Reperfusion Are Attenuated by κ-Opioid Receptor Agonist

Background and Aims ains unclear whether U50488H (a selective κ-opioid receptor agonist) produces anti-apoptotic effect during ischemia and reperfusion (I/R). Therefore, the effect of U50488H on myocardial apoptosis was investigated in the present study. s ere subjected to 45 min coronary artery occlusion and 180 min of reperfusion. U50488H (1.5 mg/kg IV) was given prior to occlusion. Nor-Binaltorphimine (nor-BNI) (2 mg/kg IV), a selective κ-opioid receptor antagonist, was given 10 min prior to U50488H. Cardiac apoptosis was evaluated by terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling (TUNEL) assay and in situ identification of nuclear DNA fragmentation. s trastructure injury of myocardium, myocardial infarct size, and plasma CK and LDH were reduced significantly with administration of U50488H before I/R, whereas the effects of U50488H were abolished by nor-BNI. DNA fragments were visualized by agarose electrophoresis, and clear DNA ladder formation was observed in myocardial tissue from hearts subjected to I/R. Administration of U50488H before ischemia exerted a significant anti-apoptotic effect as evidenced by markedly weaker DNA ladder formation. TUNEL staining showed U50488H treatment before I/R significantly reduced the percentage of apoptotic cells, which was blocked by 5-HD, a mitochondrial kATP channel blocker. In accordance, U50488H treatment significantly inhibited I/R-induced elevated activities of caspase-3 and caspase-9. U50488H also produced an increase in Bcl-2 and a decrease in Bax protein expression in the I/R heart, and the anti-apoptotic effects of U50488H were all blocked by nor-BNI. sions H reduces myocardial necrosis and apoptosis after I/R and activation of κ-opioid receptor may mediate a role in U50488H-induced myocardial protection.