Nociceptin receptor activation produces nitric oxide-mediated systemic hypotension

The purpose of the present study was to investigate the effects of L-N-5-(1 -iminoethyl)ornithine hydrochloride (L-NIO), an inhibitor of nitric oxide ( NO) formation, and [Phe(1)-Psi(CH2NH)-Gly(2)]Nociceptin(1-13)-NH2 (Phe-NOC) , a nociceptin receptor antagonist, on the systemic vasodepressor response to nociceptin in the anesthetized rat. The systemic vasodepressor response to bolus intravenous (i.v.) injections of nociceptin was significantly redu ced by L-NIO and Phe-NOC. The present data suggest activation of nociceptin receptors dilates the systemic vascular bed through a NO-dependent pathway . These data also demonstrate Phe-NOC is an efficacious and selective nocic eptin receptor antagonist in vivo. (C) 1999 Elsevier Science Inc.