Cardiovascular Effects of Nociceptin in Unanesthetized Mice

摘要: We evaluated the systemic hemodynamic effects induced by nociceptin (NC) and NC-related peptides, including NC receptor antagonist [Phe1psi(CH2-NH)Gly2]NC(1-13)NH2 ([F/G]NC(1-13)NH2) in unanesthetized normotensive Swiss Morini mice. Bolus intravenous injection of decreased mean blood pressure heart rate. The hypotensive response to 10 nmol/kg lasted <10 minutes, whereas a more prolonged hypotension was evoked 100 (from 114+/-3 97+/-2 mm Hg at P<0.01). latter dose reduced rate from 542+/-43 479+/-31 beats/min (P<0.05) increased aortic flow 41+/-5% (P<0.05). Hypotension bradycardia were also NC(1-17)NH2 NC(1-13)NH2 fragments, NC(1-13)OH NC(1-9)NH2 ineffective. Thiorphan, an inhibitor neutral endopeptidase 24.11, enhanced revealed ability decrease pressure. [F/G]NC(1-13)NH2, recently synthesized receptor, did not alter basal or rate, but it prevented hypotension, bradycardia, increase NC. In contrast, [F/G]NC(1-13)NH2 bradykinin endomorphin-1 (a micro-receptor agonist), leu-enkephalin delta-receptor agonist) U504885 synthetic kappa-receptor agonist). conclusion, some its fragments cause mice, with NC(1-13) sequence being critical for these biological effects. Our results demonstrate that compound is potent selective vivo.