We examined the combined effects of the
calcium channel blockers 1,4-dihydropyridine (
benidipine) and benzothiazepine (
diltiazem) on cardiohemodynamics in anesthetized dogs.
Benidipine (3 microg/kg) lowered blood pressure (BP) slightly and continuously increased coronary flow (CF).
Diltiazem (300, 1000 microg/kg) decreased BP, heart rate (HR), and the maximum rate of rise of left ventricular pressure (LV dP/dt max) with the increase of doses.
Diltiazem increased CF, though it was transient when compared to
benidipine. A combination of
benidipine (3 microg/kg) and
diltiazem (300 microg/kg) showed continuous decreases in BP, HR, and LV dP/dt max, and an increase in CF that was similar to that recorded for the
benidipine group. The level of double product (DP: systolic BPxHR, an index of myocardium energy consumption) in the combination group was significantly lower than that of the
benidipine group. The plasma concentrations of
benidipine and
diltiazem in the combination group were similar to those of the groups receiving either
drug. These results demonstrate that the combination of
benidipine and
diltiazem increases CF more continuously than
diltiazem alone, and decreases DP more potently than
benidipine alone, indicating that the combination
therapy possesses favorable properties as a treatment for
angina pectoris. Therefore, the combination of
benidipine and
diltiazem is suggested as a useful treatment for improving the clinical benefits of monotherapy for angina, compared with the use of
diltiazem alone at higher doses.