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

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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

Fingerprint

Bradycardia
Controlled Hypotension
Hypotension
Blood Pressure
Thiorphan
Heart Rate
Artificial Receptors
nociceptin
Leucine Enkephalin
Neprilysin
Opioid Receptors
Bradykinin
nociceptin (1-13) amide
Intravenous Injections
Hemodynamics
Peptides
nociceptin receptor

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.

Cardiovascular effects of nociceptin in unanesthetized mice. / Madeddu, Paolo; Salis, Maria Bonaria; Milia, Anna Franca; Emanueli, Costanza; Guerrini, Remo; Regoli, Domenico; Calò, Girolamo.

In: Hypertension, Vol. 33, No. 3, 03.1999, p. 914-919.

Research output: Contribution to journalArticle

Madeddu, P, Salis, MB, Milia, AF, Emanueli, C, Guerrini, R, Regoli, D & Calò, G 1999, 'Cardiovascular effects of nociceptin in unanesthetized mice', Hypertension, vol. 33, no. 3, pp. 914-919.
Madeddu P, Salis MB, Milia AF, Emanueli C, Guerrini R, Regoli D et al. Cardiovascular effects of nociceptin in unanesthetized mice. Hypertension. 1999 Mar;33(3):914-919.
Madeddu, Paolo ; Salis, Maria Bonaria ; Milia, Anna Franca ; Emanueli, Costanza ; Guerrini, Remo ; Regoli, Domenico ; Calò, Girolamo. / Cardiovascular effects of nociceptin in unanesthetized mice. In: Hypertension. 1999 ; Vol. 33, No. 3. pp. 914-919.
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