title: Bradykinin B2 receptor-mediated chronotropic effect of bradykinin in isolated guinea pig atria.
abstract: The present study was undertaken to characterize the direct chronotropic effect of bradykinin in isolated spontaneously beating atria of the guinea pig. Bradykinin caused concentration-dependent increases in the beating rate of atria. In contrast, the active metabolite of bradykinin and the typical bradykinin B1 receptor agonist, Des-Arg9-bradykinin, had no effect on the beating rate of atria. Inhibition of converting enzyme or neutral endopeptidase by captopril or SQ-28603, respectively, did not affect beating rate but potentiated bradykinin-induced increase in beating rate. The potent bradykinin B2 receptor antagonist, HOE 140, antagonized bradykinin-induced chronotropic effect. In contrast, the bradykinin B1 receptor antagonist, Lys-[Leu8]Des-Arg9-bradykinin, had no effect. The increase in beating rate caused by bradykinin was not affected by blockade of beta 1-adrenoceptors, cyclooxygenase, or nitric oxide synthesis using atenolol, indomethacin and N omega-nitro-L-arginine, respectively. Unlike bradykinin, angiotensin I and angiotensin II caused very small or no change in beating rate in the presence or absence of captopril and SQ-28603. These results indicate that bradykinin causes a direct positive chronotropic effect which is mediated by activation of bradykinin B2 receptors independently of prostaglandins and beta 1-adrenoceptors.
authors.affiliation: Department of Pharmacology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ, USA.
authors.forename: B
authors.initials: B
authors.lastname: Tesfamariam
authors.forename: G T
authors.initials: GT
authors.lastname: Allen
authors.forename: J R
authors.initials: JR
authors.lastname: Powell
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000409:Alanine / Q000031:analogs & derivatives / Q000494:pharmacology; D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D016275:Atrial Function; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology*; D065168:Bradykinin Receptor Antagonists; D002216:Captopril / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D007609:Kallidin / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000648:ultrastructure; D009569:Nitric Oxide / Q000502:physiology; D011453:Prostaglandins / Q000502:physiology; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000819:agonists*; D012680:Sensitivity and Specificity
chemical_list: D000318:Adrenergic beta-Agonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D065168:Bradykinin Receptor Antagonists; D004791:Enzyme Inhibitors; D011453:Prostaglandins; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; C082229:bradykinin, Lys-Leu(8)-desArg(9)-; C065359:SQ 28603; D000804:Angiotensin II; D009569:Nitric Oxide; D007609:Kallidin; C065679:icatibant; D000803:Angiotensin I; D002216:Captopril; D000409:Alanine; D001920:Bradykinin