BRADYKININ B-2 RECEPTOR-MEDIATED CHRONOTROPIC EFFECT OF BRADYKININ IN ISOLATED GUINEA-PIG ATRIA

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 B-1 receptor agonist, Des-Arg(9)-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 B-2 receptor antagonist, HOE 140, antagonized bradykinin-induced chronotropic effect. In contrast, the bradykinin B-1 receptor antagonist, Lys-[Leu(8)]Des-Arg(9)-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 B-2 receptors independently of prostaglandins and beta(1)-adrenoceptors.