Increased cardiac tolerance to ischemia/reperfusion by delta 2 opioid receptor receptor Deltorphin‐B mediated by NO‐synthase, protein kinase C and tyrosine kinase

Abstract

We investigated the contribution of NO‐synthase (NOS), protein kinase C (PKC), tyrosine kinase (TK) and potassium ATP (KATP) channel activation to the mechanism(s) of antiarrhythmic action of the selective δ2 opioid receptor (OR) agonist Deltorphin‐B (Delt‐B). Delt‐B was administered to rats 15 min prior to coronary artery occlusion (45 min) and 10 min reperfusion. Pretreatment with Delt‐B (150 nmol/kg) significantly reduced the incidence of ischemia and reperfusion induced arrhythymias. The NOS inhibitor, L‐NAME, the TK inhibitor, genistein, the PKC inhibitor, chelerythrin, the non‐selective KATP channel inhibitor, glibenclamide, and the selective mitochondrial KATP inhibitor 5‐hydroxydecanoate (5‐HD) were also administered prior to coronary artery occlusion. PKC, TK, and NOS inhibitors blocked the arrhythmogenic protection during ischemia/reperfusion provided by peripheral δ2 activation by Delt‐B. The KATP blockers glibenclamide and 5‐HD did not abolish the protective effect of Delt‐B. The inhibitors alone were without effect. We conclude that the antiarrhythmic ischemic protection of Delt‐B is mediated in part by mechanism relying on activation of PKC, TK and NOS and does not rely on KATP channel activation. Supported by a VA Merit Review Grant (SAB), Office of Navel Research (PRO) and the Russian Foundation of Basic Research (LNM).