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Cardiovascular effects of nociceptin in unanesthetized mice

Madeddu, Paolo Roberto and Salis, Maria Bonaria and Milia, Anna Franca and Emanueli, Costanza and Guerrini, Remo and Regoli, Domenico and Calò, Girolamo (1999) Cardiovascular effects of nociceptin in unanesthetized mice. Hypertension, Vol. 33 (3), p. 914-919. eISSN 1524-4563. Article.

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Abstract

We evaluated the systemic hemodynamic effects induced by nociceptin (NC) and NC-related peptides, including the NC receptor antagonist [Phe1Ψ(CH2-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, P<0.01). The latter dose reduced heart rate from 542±43 to 479±31 beats/min (P<0.05) and increased aortic blood flow by 41±5% (P<0.05). Hypotension and bradycardia were also evoked by NC(1–17)NH2 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.

Item Type:Article
ID Code:884
Status:Published
Refereed:Yes
Uncontrolled Keywords:Hypotension, blood pressure, heart rate, nociceptin, [Phe1Ψ(CH2-NH)Gly2]NC(1–13)NH2, mouse
Subjects:Area 05 - Scienze biologiche > BIO/14 Farmacologia
Area 06 - Scienze mediche > MED/09 Medicina interna
Divisions:001 Università di Sassari > 03 Istituti > Clinica medica generale e terapia medica
002 Altri enti e centri di ricerca del Nord Sardegna > National laboratory of the national institute of biostructures and biosystems, Osilo
Publisher:Lippincott Williams & Wilkins
eISSN:1524-4563
Copyright Holders:© 1999 American Heart Association
Deposited On:18 Aug 2009 10:03

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