title: Bradykinin B2-receptor-mediated positive chronotropic effect of bradykinin in isolated rat atria.
abstract: The positive chronotropic effect of bradykinin was investigated in isolated spontaneously beating atria of the rat. Cumulative additions of bradykinin (0.3-100 nM) caused a concentration-dependent increase in the beating rate of the atria by maximally 35+/-4 beats/min, approximately 25% of the 1 microM isoprenaline-induced maximal responses. In contrast, the active metabolite of bradykinin and selective bradykinin B1-receptor agonist, Des-Arg9-bradykinin, did not influence the spontaneous frequency of beating. Propranolol (1 microM) combined with prazosin (1 microM) did not affect the positive chronotropic effect of bradykinin. A selective bradykinin B2-receptor antagonist, Hoe 140, concentration-dependently shifted the response curves for bradykinin to the right, whereas the bradykinin B1-receptor antagonist, Lys-[Leu8]Des-Arg9-bradykinin had no effect. The tachycardic responses to bradykinin were potentiated by ramipril, an angiotensin-converting enzyme/kininase II inhibitor, but not affected by Nomega-nitro-L-arginine methyl ester hydrochloride, a nitric oxide synthesis inhibitor. Indomethacin and meclofenamate, two cyclooxygenase inhibitors, abolished the bradykinin-induced chronotropic effect. These results indicate that exogenous bradykinin induces a positive chronotropic effect that occurs independent of adrenoceptors. The bradykinin-induced chronotropic effect is mediated by bradykinin B2 receptors, whereas B1 receptors do not play a role in mediating this effect. Prostaglandins but not nitric oxide appear to be involved in bradykinin-induced positive chronotropic effect.
authors.affiliation: Department of Pharmacotherapy, University of Amsterdam, The Netherlands.
authors.forename: Q
authors.initials: Q
authors.lastname: Li
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: J F
authors.initials: JF
authors.lastname: Loro
authors.forename: M
authors.initials: M
authors.lastname: Pfaffendorf
authors.forename: P A
authors.initials: PA
authors.lastname: van Zwieten
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000502:physiology*; D013268:Stimulation, Chemical
chemical_list: D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; D009569:Nitric Oxide; D001920:Bradykinin; D007213:Indomethacin