INFARCT-REDUCING EFFECT OF DELTORPHIN II IN REPERFUSION OF THE HEART. THE ROLE OF NO-SYNTHASE, GUANYLYLCYCLASE, cGMP, MPT PORE

Highlights The selective δ 2 -opioid receptor agonist deltorphin II increases cardiac tolerance to reperfusion by activating guanylyl cyclase, stimulating cGMP synthesis, activating sarcK ATP channel, and blocking MPT pore. Aim . To evaluate the role of NO-synthase, guanylyl cyclase, cGMP, MPT pore in the infarct-limiting effect of deltorphin II in the model of ischemia and reperfusion of the rat heart. Methods . Coronary artery occlusion (45 min) and reperfusion (2 h) were performed in rats anesthetized with chloralose. The selective δ 2 -opioid receptor agonist deltorphin II was administered intravenously at a dose of 120 µg/kg 5 min before reperfusion. The NO synthase inhibitor L-NAME, the guanylyl cyclase inhibitor ODQ, and the MPT pore blocker atractyloside were administered intravenously 10 min before reperfusion. The cAMP and cGMP levels were measured in myocardial tissue. Results . Deltorphin II causes a decrease in infarct size by about 50%. L-NAME did not affect the cardioprotective effect of deltorphin. Atractyloside and ODQ completely abolished the infarct-reducing effect of deltorphin. Deltorphin II caused an increase in the cGMP level in the myocardium, but did not affect the cAMP level. Conclusion . Analysis and generalization of obtained data and the results of previous studies indicate that the infarct-limiting effect of deltorphin II is associated with activation of δ 2 -opioid receptors located in cardiomyocytes, followed by activation of heme oxygenase-1, an increase in CO production, stimulation of guanylyl cyclase, and activation of protein kinase G. The putative end-effectors are MPT pore and sarcK ATP channel. In turn, NO synthase is not involved in signal transduction from δ 2 -OR to the MPT pore and sarcK ATP channel.