Significance of opioid receptors in regulation of cardiac tolerance in pathogenic impact of long-term ischemia-reperfusion in vivo
Maslov, L.N.; Barzakh, E.I.; Krylatov, A.V.; Brown, S.A.; Oeltgen, P.R.; Govindaswami, M.; Chernysheva, G.A.; Solenkova, N.V.; Lishmanov, A.I.; Tsibul'nikov, S.I.; Krieg, T.; Zhang, E.
Rossiiskii Fiziologicheskii Zhurnal Imeni I.M. Sechenova 95(6): 563-572
2009
ISSN/ISBN: 0869-8139 PMID: 19639880 Document Number: 632482
The study aimed at investigation of the role of opioid receptor (OR) in regulation of cardiac tolerance to ischemia-reperfusion. Opioid receptor ligands and inhibitors were administered in vivo prior to coronary artery occlusion (45 min) and reperfusion (2 hrs). Occurring infraction size/area at risk (IS/AAR) ratio was determined. Pretreatment with the micro-OR agonists DAMGO and dermorphin H exerted no effect on the IS/AAR ratio. Activation of delta 1-OR by DPDPE did not alter cardiac tolerance in ischemia-reperfusion either. Pretreatment with the delta 2-OR agonists deltorphin D and deltorphin E or ORL1 receptor agonist nociceptin exerted no effect on the IS/AAR ratio. Stimulation of K-OR by selective agonists did not modify cardiac tolerance to ischemia-reperfusion. The delta 2-OR agonist deltorphin II significantly reduced the IS/AAR index. This effect was prevented by treatment with naltrexone, naloxone methiodide and the delta 2-OR antagonist naltriben but not by the delta 1-OR antagonist BNTX. The infarction-limiting effect of deltorphin II was also abolished by inhibition of protein kinase C (PKC) and mitochondrial Katp channels. Thus, the agonists of micro, delta 1, kappa, and ORL1 receptors in used doses did not affect cardiac tolerance in ischemia-reperfusion injury in vivo. The peripheral delta 2-OR activation induces infarction size reduction. Its infarction-reducing effect of deltorphin II is mediated via PKC activation and mitochondrial Katp, channel opening.