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

Highlights

The selective δ₂-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 δ₂-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 δ₂-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 δ₂-OR to the MPT pore and sarcK_ATP channel.

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