Intrinsic and reflex actions of verapamil and nifedipine: assessment in normal subjects by noninvasive techniques and autonomic blockade

Abstract

To determine the intrinsic and reflex activities of calcium antagonists, 8 healthy volunteers were administered single doses of verapamil 10 mg i.v. and nifedipine 20 mg sublingually alone and during autonomic blockade (atropine 0.04 mg/kg and propranolol 0.2 mg/kg). Heart rate, PQ-time, systolic time intervals, blood pressure, and left ventricular echocardiograms were used to measure the pharmacodynamic effects, which were evaluated by multivariate analysis of variance. In general the effects of verapamil were most distinct when the 10-min infusion ended, while nifedipine acted after a latent period of 9 minutes. Both calcium antagonists given alone induced almost identical increases in heart rate and cardiac output and decreases in total peripheral resistance. Nifedipine also reduced systolic wall stress and increased fractional shortening, while verapamil prolonged systolic time intervals and PQ-time and reduced fractional shortening. During autonomic blockade, nifedipine no longer had a significant effect on these parameters. However, after the blockade verapamil led to marked decrease in heart rate, cardiac output, blood pressure and systolic wall stress; total peripheral resistance and fractional shortening were not changed, and the systolic time intervals and PQ-time were prolonged as after verapamil alone. It is concluded that both calcium antagonists stimulate distinct sympathetic reflexes, which may modify or even reverse their intrinsic actions. The effects of nifedipine on the cardiovascular system are considered to result from a reduction in peripheral vascular tone, whereas the effects of verapamil can be attributed to cardiac (negative inotropic, chronotropic and dromotropic) and peripheral vascular actions.