Cardiovascular Effects of Nicardipine in Anesthetized Open-Chest Dogs in the Absence and Presence of β-Adrenergic Receptor Blockade: A Comparison with Nifedipine and Verapamil

Nicardipine, a new 1,4-dihydropyridine calcium-entry blocker, was assessed for cardiovascular effects against nifedipine and verapamil in anesthetized open-chest beagle dogs, in the absence and presence of β-adrenoceptor blockade (propranolol 1 mg/kg i.v.). In control conditions, intravenous nicardipine and nifedipine (30 nmol/kg) produced decreases in blood pressure of similar magnitude without evidence of cardiodepression. An equihypotensive dose of verapamil (300 nmol/kg), by contrast, induced long-lasting negative chronotropic and inotropic effects, which, when combined with the effects of propranolol, were so marked as to cause the death of two of five dogs (atrioventricular block). Dihydropyridine derivatives at higher doses (100 nmol/kg) produced different responsesnifedipine depressed cardiac performance significantly more than nicardipine and, in the presence of β-adrenergic blockade, caused the death of three of six dogs due to cardiovascular failure. In the nicardipine group, on the contrary, cardiac function was adequately preserved even in the presence of β-blocker, and no animals died. The results of the present study confirm a previous in vitro observationnicardipine is a calcium-entry blocker devoid of remarkable cardiodepressant effects and particularly selective for the vascular smooth muscle.