EFFECT OF CALCIUM-ANTAGONISTS ON PLASMA NOREPINEPHRINE LEVELS, HEART-RATE, AND BLOOD-PRESSURE

To evaluate the effects of calcium antagonists on sympathetic: activit y in hypertensive patients, a MEDLINE search for English language arti cles published between 1975 and May 1996 using the terms calcium antag onists, sympathetic nervous system, and catecholamines was conducted, Clinical studies only reporting the effects of calcium antagonists on blood pressure, heart rate, and plasma norepinephrine (NE) levels in p atients with hypertension were included, Data were combined and analyz ed according to class of calcium antagonist (dihydropyridine vs nondih ydropyridine), their duration of action (short-acting [SA] vs long-act ing [LA]), and treatment duration, We identified 63 studies involving 1,252 patients, Acutely after single dosing, SA calcium antagonists de creased mean arterial pressure by 13.7 +/- 1.1% and increased heart ra te by 13.7 +/- 1.4% and NE levels by 28.6 +/- 2.5%, Change in NE level s correlated with change in heart rate (r = 0.59, p <0.01) and inverse ly with change in arterial pressure (r = 0.46, p <0.05) in patients ta king dihydropyridine calcium antagonists acutely. With sustained thera py, both classes of SA calcium antagonists increased NE levels. Wherea s NE levels remained slightly elevated and heart rate unchanged with L A dihydropyridine calcium antagonists, both heart rate and NE levels d ecreased with LA nondihydropyridine calcium antagonists, SA calcium an tagonists stimulate sympathetic activity when given acutely and over t he long term, irrespective of their molecular structure. Sympathetic a ctivation is less pronounced with LA dihydropyridine calcium antagonis ts and decreases with LA nondihydropyridine calcium antagonists. These data offer a possible pathophysiologic explanation for the increase i n morbidity and mortality observed in some studies using SA calcium an tagonists. (C) 1997 by Excerpta Medica, Inc.