The relaxant effect of nociceptin on porcine coronary arterial ring segments

Nociceptin (NC), alias orphanin FQ, has been identified as the endogenous ligand of the opioid receptor-like 1 receptor (ORL1). The purpose of this study was to assess the effect of nociceptin on porcine coronary arteries and to investigate the mechanism of its action, if any. Rings of coronary arteries from porcine hearts were suspended in baths containing Krebs solution, and isometric tension was measured. The response to nociceptin (10(-12)-10(-5) mol/L) was investigated in porcine coronary arterial rings and also in such rings contracted with prostaglandin F-2alpha (PGF(2alpha)). The effects of endothelium, nitroxide (NO), methylene blue, cyclic GMP (cGMP), naloxone, [Nphe(1)]NC(1-13)NH2, and propranolol on nociceptin-induced relaxation were also assessed. Our study showed nociceptin relaxed the porcine coronary arterial rings and inhibited the vasocontractivity to PGF(2alpha). The relaxing response of nociceptin in coronary arteries was significantly reduced by removal of endothelium and by the presence of L-NNA, cGMP, and [Nphe(1)]NC(1-13)NH2, the selective nociceptin receptor antagonist, but not by naloxone, the nonselestive opioid receptor blocker or propranolol, which blocks the adrenergic P-receptor. Our results suggest that nociceptin induces relaxation of isolated coronary artery through NO, cGMP, and ORL1.