Effect of calcium antagonists on plasma norepinephrine levels, heart rate, and blood pressure.

To evaluate the effects of calcium antagonists on sympathetic activity in hypertensive patients, a MEDLINE search for English language articles published between 1975 and May 1996 using the terms calcium antagonists, 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 patients with hypertension were included. Data were combined and analyzed according to class of calcium antagonist (dihydropyridine vs nondihydropyridine), their duration of action (short-acting [SA] vs long-acting [LA]), and treatment duration. We identified 63 studies involving 1,252 patients. Acutely after single dosing, SA calcium antagonists decreased mean arterial pressure by 13.7 +/- 1.1% and increased heart rate by 13.7 +/- 1.4% and NE levels by 28.6 +/- 2.5%. Change in NE levels correlated with change in heart rate (r = 0.59, p <0.01) and inversely with change in arterial pressure (r = 0.46, p <0.05) in patients taking dihydropyridine calcium antagonists acutely. With sustained therapy, both classes of SA calcium antagonists increased NE levels. Whereas NE levels remained slightly elevated and heart rate unchanged with LA dihydropyridine calcium antagonists, both heart rate and NE levels decreased with LA nondihydropyridine calcium antagonists. SA calcium antagonists stimulate sympathetic activity when given acutely and over the long term, irrespective of their molecular structure. Sympathetic activation is less pronounced with LA dihydropyridine calcium antagonists and decreases with LA nondihydropyridine calcium antagonists. These data offer a possible pathophysiologic explanation for the increase in morbidity and mortality observed in some studies using SA calcium antagonists.