BRADYKININ B-2-RECEPTOR-MEDIATED POSITIVE CHRONOTROPIC EFFECT OF BRADYKININ IN ISOLATED RAT ATRIA

The positive chronotropic effect of bradykinin was investigated in iso lated spontaneously beating atria of the rat. Cumulative additions of bradykinin (0.3-100 nM) caused a concentration-dependent increase in t he beating rate of the atria by maximally 35 +/- 4 beats/min, similar to 25% of the 1 mu M isoprenaline-induced maximal responses. In contra st, the active metabolite of bradykinin and selective bradykinin B-1-r eceptor agonist, Des-Arg(9)-bradykinin, did not influence the spontane ous frequency of beating. Propranolol (1 mu M) combined with prazosin (1 mu M) did not affect the positive chronotropic effect of bradykinin . A selective bradykinin B-2-receptor antagonist, Hoe 140, concentrati on-dependently shifted the response curves for bradykinin to the right , whereas the bradykinin B-1-receptor antagonist, Lys-[Leu(8)]Des-Arg( 9)-bradykinin had no effect. The tachycardic responses to bradykinin w ere potentiated by ramipril, an angiotensin-converting enzyme/kininase II inhibitor, but not affected by N-omega-nitro-L-arginine methyl est er hydrochloride, a nitric oxide synthesis inhibitor. Indomethacin and meclofenamate, two cyclooxygenase inhibitors, abolished the bradykini n-induced chronotropic effect. These results indicate that exogenous b radykinin induces a positive chronotropic effect that occurs independe nt of adrenoceptors. The bradykinin-induced chronotropic effect is med iated by bradykinin B-2 receptors, whereas B-1 receptors do not play a role in mediating this effect. Prostaglandins but not nitric oxide ap pear to be involved in bradykinin-induced positive chronotropic effect .