Role of nitric oxide in mediating vasodilator responses to opioid peptides in the rat

Hunter C. Champion, Trinity J. Bivalacqua, James E. Zadina, Abba J. Kastin, Albert L. Hyman, Philip J. Kadowitz

Research output: Contribution to journalArticlepeer-review

Abstract

1. Endomorphins 1 and 2, endogenous ligands for the μ-opioid receptor, and nociceptin (orphanin FQ; OFQ), an endogenous ligand for the ORL1 receptor, have vasodilator activity in the vascular bed of the hindquarters of the rat. In the present study, the role of nitric oxide (NO), vasodilator prostaglandins and the opening of KATP channels in mediating vasodilator responses to these novel agonists was investigated in the rat. 2. Under constant-flow conditions, injections of endomorphins 1 and 2, PL017 ([N-MePhe3,D-Pro4]-morphiceptin), nociceptin and Tyr-D-Ala-Gly-MePhe-Gly(ol)-enkephalin (DAMGO) produced dose-dependent decreases in hindquarters perfusion pressure. Vasodilator responses to endomorphin 1 and 2, acetylcholine and adrenomedullin, were attenuated by the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) at a time when vasodilator responses to nociceptin, adreno-medullin and the NO donor diethylamine/NO were not altered. 3. Vasodilator responses to endomorphins 1 and 2, nociceptin, PL017 and DAMGO were not altered after administration of sodium meclofenamate at a time when vasodilator responses to arachidonic acid were reduced significantly or after administration of U-37883A at a time when vasodilator responses to levcromakalim were reduced significantly. 4. The results of these studies indicate that vasodilator responses to endomorphins 1 and 2, PL017 and DAMGO are mediated, in large part, by the release of NO, whereas vasodilator responses to nociceptin are mediated by an L-NAME-insensitive mechanism. Moreover, these results demonstrate that the vasodilator responses to these peptides are not due to the release of vasodilator prostaglandins or the opening of KATP channels in the hindquarters vascular bed of the rat.

Original languageEnglish (US)
Pages (from-to)229-232
Number of pages4
JournalClinical and Experimental Pharmacology and Physiology
Volume29
Issue number3
DOIs
StatePublished - 2002
Externally publishedYes

Keywords

  • Endomorphin
  • Nitric oxide
  • Nociceptin
  • Rat
  • Regional vasculature

ASJC Scopus subject areas

  • Physiology
  • Pharmacology
  • Physiology (medical)

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