Divergent effects of verapamil and amlodipine at rest and during exercise

To evaluate, in healthy volunteers, the effects of acute administration of two calcium antagonists with different pharmacological profiles, verapamil and amlodipine, on haemodynamics at rest and during exercise.

Six healthy volunteers (aged 20-29 years) 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 pressures (measured using a cuff sphygmomanometer), heart rate (HR), cardiac index (CI, bioimpedance), rate-pressure product (SAP x HR), and noradrenaline 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) started 3 h after drug administration.

At rest arterial pressure, HR, rate-pressure product and catecholamine plasma levels did not change after verapamil or amlodipine administration, whereas CI significantly decreased after verapamil (from 3.9 +/- 0.4 to 3.3 +/- 0.4 l/min per m2) but not after amlodipine (3.9 +/- 0.3 and 4.1 +/- 0.5 l/m per m2) administration. During exercise the increases in SAP and HR were slightly but not significantly higher after amlodipine than after verapamil administration, rate-pressure product and CI were higher after amlodipine (22 +/- 1 x 10(3) mmHg x beats/min and 13 +/- 2 l/min per m2, respectively) than after verapamil (20 +/- 1 x 10(3) mmHg x beats/min and 10 +/- 2 l/min per m2, respectively) administration. Plasma levels of noradrenaline and adrenaline were similar at rest after each treatment and were slightly more increased after amlodipine administration during exercise.

In contrast to amlodipine, verapamil induced a slight myocardial depressive effect at rest and did not potentiate 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 exercise.