DIVERGENT EFFECTS OF DIHYDROPYRIDINE AND PHENYLALKYLAMINE CALCIUM-CHANNEL ANTAGONIST CLASSES ON AUTONOMIC FUNCTION IN HUMAN HYPERTENSION

Calcium channel antagonists differ by class in reported frequency of s ide effects that suggest reflex sympathoadrenal activation. Do such di fferences result from differential effects on autonomic and baroreflex function? The present study compared acute and chronic effects of two classes of calcium channel antagonists, the dihydropyridine type (fel odipine) and the phenylalkylamine type (verapamil), on efferent sympat hetic outflow and baroreflex slope in 15 essential hypertensive subjec ts. Blood pressure, heart rate, hemodynamics, and biochemistries were determined at baseline and after acute (first dose) and chronic (4 wee ks) administration of the drugs versus placebo. Acutely, felodipine ca used a greater decrease in blood pressure associated with a larger dec line in systemic vascular resistance than the corresponding effects pr oduced by verapamil. Chronically, there were similar, significant decl ines in blood pressure (P=.001) and systemic vascular resistance (P=.0 01) after each drug. Acutely, increased sympathetic activity after fel odipine was suggested by reflex tachycardia (from 69+/-3 to 74+/-2 bea ts per minute, P=.014) and elevation of plasma norepinephrine (from 26 4+/-25 to 323+/-25 pg/mL, P=.037), whereas after verapamil the corresp onding changes were closely similar to those after placebo. Chronicall y, verapamil suppressed sympathetic activity, as evidenced by a decrea se in resting heart rate (from 76+/-2 to 69+/-3 beats per minute, P=.0 02), decrease in plasma norepinephrine (from 264+/-25 to 178+/-21 pg/m L, P<.001), decrease in chromogranin A (from 33.0+/-2.4 to 27.8+/-1.7 ng/mL, P<.001), and lessened response of mean arterial pressure (P=.00 6) and heart rate (P=.016) to phentolamine cu-adrenergic blockade. aft er chronic felodipine, all of these variables were unchanged. Neither drug affected baroreflex slope. We conclude that felodipine and verapa mil have qualitatively different, time-dependent actions on efferent s ympathetic nervous system activity, actions that may in part explain t he disparity in autonomic/hemodynamic side effect profiles of the dihy dropyridine and phenylalkylamine classes of calcium channel antagonist s.