Inhibition of cardiovascular activity following microinjection of novel opioid-like neuropeptide nociceptin (orphanin FQ) into the rat rostral ventrolateral medulla

Nociceptin (orphanin FQ), the newly discovered endogenous ligand for the no vel opioid receptor-like 1 receptor, has been initially found to participat e in pain modulation. In this study, centrally mediated cardiovascular acti ons of this peptide were investigated in the alpha-chloralose/urethane-anes thetized rats. We found that bilateral injection of nociceptin (10 nmol) in to the rostral ventrolateral medulla (RVLM), wherein injection of excitator y amino acid DL-homocysteic acid (3 nmol) induced typical presser responses , significantly reduced arterial blood pressure and heart rate by -32% and -15%, respectively. Reduction of blood pressure and heart rate in response to intra-RVLM injection of nociceptin was dose-dependent with a threshold d ose being 3 nmol. Pretreatment with the selective nociceptin receptor antag onist, [Phe(psi)(1)(CH2-NH)Gly(2)]NC(1-13)NH2 (10 nmol), into the RVLM abol ished the nociceptin-induced cardiovascular inhibition. In contrast, non-se lective opioid receptor antagonist, naloxone (10 nmol), did not modify the hypotension and bradycardia induced by nociceptin, even though naloxone at the same dose prevented reduction of blood pressure and heart rate induced by intra-RVLM injection of methionine-enkephalin (3 nmol). Both [Phe(psi)(1 )(CH2-NH)Gly(2)]NC(1-13)NH2 and naloxone injection alone had no significant effect on baseline blood pressure and heart rate. These data suggest that the newly discovered opioid-like neuropeptide nociceptin in the CNS exert p owerful influence on hemodynamic activity by affecting the RVLM neurons. Th is influence is inhibitory in nature, which may not be active in normal phy siological conditions. Moreover, the cardiovascular effects of nociceptin w ere mediated by activation of specific nociceptin receptors rather than typ ical naloxone-sensitive opioid receptors. (C) 1999 Elsevier Science B.V. Al l rights reserved.