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Effects of bradykinin on SA node pacemaker activity and atrial contractility were studied, using isolated, blood-perfused dog atrium preparations. Bradykinin (0.1--100 micrograms) caused a slightly but consistently positive chronotropic action, although it did not produce a consistent inotropic action. When successive doses of bradykinin were given in a short period, these preparations displayed tachphylaxis. Bradykinin-induced action was not suppressed by a potent beta-adrenoceptor blocking agent, carteolol. In addition, kallikrein (0.1--3 units), was administered into the sinus node artery to investigate the effect of endogenous kinins. Kallikrein had no effect on SA node pacemaker activity nor atrial contractility at any examined doses. On the other hand, a kallikrein inhibitor, aprotinin, induced dose-relatedly a negative inotropic and chronotropic effect at a dose range from 100 to 3,000 units. These negative actions of aprotinin were not blocked by an adequate dose of atropine. From these results, it is concluded that bradykinin has a slight direct positive chronotropic effect, and that aprotinin has direct negative inotropic and chronotropic effects in the isolated, blood-perfused canine atrium in a wide dose range.

Chronotropic and Inotropic Effects of Bradykinin on Isolated, Blood-perfused Canine Atrium