DIVERGENT EFFECTS OF VERAPAMIL AND AMLODIPINE AT REST AND DURING EXERCISE

Objective To evaluate, in healthy volunteers, the effects of acute adm inistration of two calcium antagonists with different pharmacological profiles, verapamil and amlodipine, on haemodynamics at rest and durin g exercise. Subjects and methods Six healthy volunteers (aged 20-29 ye ars) were randomly assigned to receive single oral doses of amlodipine (5 mg), slow-release verapamil (240 mg) or a placebo during a double- blind cross-over study. Systolic (SAP), diastolic and mean arterial pr essures (measured using a cuff sphygmomanometer), heart rate (HR), car diac index (CI, bioimpedance), rate-pressure product (SAP x HR), and n oradrenaline and adrenaline plasma levels were measured at rest before drug administration, and at rest and during graded bicycle exercise ( steps of 50, 100 and 150 W during 3, 3 and 4 min, respectively) starte d 3 h after drug administration. Results At rest arterial pressure, HR , rate-pressure product and catecholamine plasma levels did not change after verapamil or amlodipine administration, whereas CI significantl y decreased after verapamil (from 3.9 +/- 0.4 to 3.3 +/- 0.4 l/min per m(2)) but not after amlodipine (3.9 +/- 0.3 and 4.1 +/- 0.5 l/m per m (2)) administration. During exercise the increases in SAP and HR were slightly but not significantly higher after amlodipine than after vera pamil administration, rate-pressure product and CI were higher after a mlodipine (22 +/- 1 x 10(3) mmHg x beats/min and 13 +/- 2 l/min per m( 2), respectively) than after verapamil (20 +/- 1 x 10(3) mmHg x beats/ min and 10 +/- 2 l/min per m(2), respectively) administration, Plasma levels of noradrenaline and adrenaline were similar at rest after each treatment and were slightly more increased after amlodipine administr ation during exercise. Conclusions In contrast to amlodipine, verapami l induced a slight myocardial depressive effect at rest and did not po tentiate the myocardial effects of the sympathetic stimulation induced by exercise. The myocardial action of verapamil is such as to induce some decrease in myocardial oxygen demand, both at rest and during exe rcise. (C) 1998 Rapid Science Ltd.