Positive chronotropic activity of bradykinin in the pithed normotensive rat

Abstract

The positive chronotropic effect of bradykinin was investigated in the pithed rat preparation. Cumulative treatment with bradykinin (0.20 nmol/kg-6.59 mu mol/kg, intravenous [iv]) caused a dose-dependent increase in heart rate (HR) by a maximum of 80 +/- 3.3 beats min(-1). In contrast, the active metabolite of bradykinin and selective bradykinin B-1-receptor agonist, [des-Arg(9)]-bradykinin did not influence the spontaneous frequency of beating. Propranolol alone reduced the bradykinin-induced increase in HR and a combination of propranolol with prazosin abolished the chronotropic effect of bradykinin. The selective bradykinin B-2 receptor antagonist, Hoe 140, dose-dependently shifted the dose-response curves of bradykinin to the right, whereas the bradykinin B1 receptor antagonist, des-Arg(10)-[Leu(9)]-kallidin proved ineffective. From our experiments it may be concluded that bradykinin induces tachycardia in the pithed rat primarily by stimulating the sympathetic ganglia leading to the release of noradrenaline, which subsequently activates cardiac beta(1)-adrenoceptors. The bradykinin-induced chronotropic effect is mediated by bradykinin B-2-receptors, whereas B-1-receptors appear not to be involved.