Chronotropic and inotropic effects of captopril on the dog heart

The effects of captopril, an inhibitor of angiotensin-converting enzyme, on sinus rate and atrial contraction were investigated in 10 isolated dog atria and in 3 intact anesthetized donor dogs. Captopril (10-1,000 micrograms) caused an increase in heart rate and the development of atrial contractile tension when injected into the sinus node artery of the isolated atrium perfused with arterial blood of the anesthetized dog. At extremely high doses (1-3 mg), captopril produced brief negative effects followed by positive ones. The positive effects were completely blocked by 10 micrograms of propranolol, after which the negative ones became more evident. The positive effects were also significantly suppressed by 30 micrograms of imipramine, whereas the negative ones were not influenced by treatment with atropine. In all 3 cases when captopril (0.3 mg/Kg) was administered intravenously to donor dogs, the blood pressure decreased and a slight tachycardia usually appeared. In contrast, no significant change was observed in sinus rate and contractile tension of isolated atria. Thus, it is concluded that only at extremely high doses does captopril cause a release of catecholamine by a tyramine-like action which may have a slight depressive action on the sinus node and contractility.