The role of reactive oxygen species and redoxsensitive protein kinases in the infarction-limiting effect of opioid peptide deltorphin II in cardiac reperfusion in rats

Abstract

Background. Mortality from acute myocardial infarction with ST-segment elevation in cardiac hospitals ranges from 4.5 to 7 %, and these data has not decreased in recent years. The most common cause of death in patients is cardiogenic shock, the likelihood of which directly depends on infarct size. It is quite clear that there is an urgent need to create drugs to limit the size of infarction and prevent the occurrence of cardiogenic shock.The aim. To evaluate the role of reactive oxygen species and redox-sensitive protein kinases in the infarction-limiting effect of opioid peptide deltorphin II in cardiac reperfusion in rats.Materials and methods. Coronary occlusion (45 min) and reperfusion (120 min) were performed in rats anesthetized with α-chloralose. The selective δ2-opioid receptor agonist deltorphin II, a hydroxyl radical scavenger 2-mercaptoprpionyl glycine (2-MPG), a superoxide radical scavenger tempol, the protein kinase Cδ (PKCδ) inhibitor rottlerin, the PI3-kinase inhibitor wortmannin, the inhibitor of ERK1/2 kinase PD98059 were injected before of reperfusion of the heart.Results. Deltorphin II contributed to a two-fold decrease in infarction size. Injection of 2-MPG, tempol, rottlerin, wortmannin, PD98059 alone had no effect on infarction size in rats. 2-MPG and tempol did not affect the infarction-reducing effect of deltorphin II. Rottlerin, wortmannin, and PD98059 eliminated the cardioprotective effect of deltorphin II.Conclusion. The infarction-reducing effect of deltorphin II does not depend on the production of superoxide radical and hydroxyl radical. Superoxide radical and hydroxyl radical do not play a significant role in reperfusion injury of the heart after coronary occlusion (45 min). PKCδ, PI3-kinase, and ERK1/2 kinase are involved in the infarction-limiting effect of deltorphin II in myocardial reperfusion.