Cardiovascular effects of nociceptin in unanesthetized mice

Paolo Madeddu, Maria Bonaria Salis, Anna Franca Milia, Costanza Emanueli, Remo Guerrini, Domenico Regoli, Girolamo Calò

Research output: Contribution to journalArticle

Abstract

We evaluated the systemic hemodynamic effects induced by nociceptin (NC) and NC-related peptides, including the NC receptor antagonist [Phe1φCH2- NH)Gly2]NC(1-13)NH2 ([F/G]NC(1-13)NH2) in unanesthetized normotensive Swiss Morini mice. Bolus intravenous injection of NC decreased mean blood pressure and heart rate. The hypotensive response to 10 nmol/kg NC lasted <10 minutes, whereas a more prolonged hypotension was evoked by 100 nmol/kg (from 114±3 to 97±2 mm Hg at 10 minutes, P2 and NC(1-13)NH2 fragments, whereas NC(1-13)OH and NC(1- 9)NH2 were ineffective. Thiorphan, an inhibitor of neutral endopeptidase 24.11, enhanced the hypotension induced by NC(1-13)NH2 and revealed the ability of NC(1-13)OH to decrease mean blood pressure. [F/G]NC(1-13)NH2, a recently synthesized antagonist of the NC receptor, did not alter basal mean blood pressure or heart rate, but it prevented the hypotension, bradycardia, and increase in aortic blood flow evoked by NC. In contrast, [F/G]NC(1- 13)NH2 did not alter the hypotension induced by bradykinin or endomorphin-1 (a μ-receptor agonist), and the bradycardia induced by leu-enkephalin (a δ- receptor agonist) or U504885 (a synthetic κ-receptor agonist). In conclusion, NC and some of its fragments cause hypotension and bradycardia and increase aortic blood flow in mice, with the NC(1-13) sequence being critical for these biological effects. Our results also demonstrate that the compound [F/G]NC(1-13)NH2 is a potent and selective antagonist of the NC receptor in vivo.

Original languageEnglish
Pages (from-to)914-919
Number of pages6
JournalHypertension
Volume33
Issue number3
Publication statusPublished - Mar 1999

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Keywords

  • [Pheφ(CH- NH)Gly]NC(1-13)NH
  • Blood pressure
  • Heart rate
  • Hypotension
  • Mouse
  • Nociceptin

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Madeddu, P., Salis, M. B., Milia, A. F., Emanueli, C., Guerrini, R., Regoli, D., & Calò, G. (1999). Cardiovascular effects of nociceptin in unanesthetized mice. Hypertension, 33(3), 914-919.