EFFECT OF AMLODIPINE AND FELODIPINE ON SYMPATHETIC ACTIVITY AND BAROREFLEX FUNCTION IN NORMAL HUMANS

Baroreflex sensitization and direct sympatholytic effects have been su ggested as contributing mechanisms to the effects of dihydropyridine c alcium channel blockers in hypertension and heart failure. In this stu dy, we tested the hypothesis that either amlodipine or felodipine woul d decrease norepinephrine levels and enhance cardiac, peripheral vascu lar, or sympathetic responses to baroreflex perturbation in healthy hu mans. Six healthy male volunteers aged 21 to 40 participated, Heart ra te, forearm blood flow, arterial pressure, and norepinephrine kinetics were assessed in the supine position, after 15 min of 60 degrees head -up tilt, after 15 min of 30 degrees head-down tilt, and after 15 min head-down tilt with phenylephrine infused to raise mean arterial press ure 10 to 15 mm Hg. Studies were conducted double-blind on 3 different days 8 to 12 h after placebo, 5 mg amlodipine, and 10 mg felodipine. Resting heart rate, mean arterial pressure, forearm vascular resistanc e, plasma norepinephrine, and norepinephrine spillover were not affect ed by amlodipine or felodipine. During upright tilt, head-down tilt, a nd phenylephrine, each variable increased and decreased as expected af ter placebo. There was no effect of either amlodipine or felodipine on any response to any maneuver. Baseline sympathetic activity as reflec ted by plasma norepinephrine and norepinephrine spillover are not alte red by either amlodipine or felodipine. Neither drug acutely sensitize s baroreflex function in normal humans over the degree of perturbation produced in these protocols.