EFFECT OF CALCIUM-ANTAGONISTS ON SYMPATHETIC ACTIVITY

Objective We evaluated the effects of calcium antagonists on sympathet ic activity in hypertensive patients by searching MedIine for English language articles published between 1975 and May 1996 using the terms calcium antagonists, sympathetic nervous system and catecholamines. Me thods Data from clinical studies reporting only the effects of calcium antagonists on blood pressure, heart rate and plasma norepinephrine ( NE) levels in patients with hypertension were analysed according to cl ass of calcium antagonist (dihydropyridine vs non-dihydropyridine), th eir duration of action (short-acting (SA) vs long-acting (LA)) and tre atment duration. Results We identified 63 studies involving 1252 patie nts. Acutely after single dosing, SA calcium antagonists decreased mea n 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 correlate d 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 dihydropyrid ine calcium antagonists acutely. With sustained therapy, both classes of SA calcium antagonists increased NE levels. Whereas NE levels remai ned slightly elevated and heart rate unchanged with LA. dihydropyridin e calcium antagonists, both heart rate and NE levels decreased with LA non-dihydropyridine calcium antagonists. SA calcium antagonists stimu late sympathetic activity when given acutely and over the long term, i rrespective of their molecular structure. In contrast, sympathetic act ivation is less pronounced with LA dihydropyridine calcium antagonists and falls with LA non-dihydropyridine calcium antagonists. Conclusion s The present finding offer a possible pathophysiological explanation for the increase in morbidity and mortablity observed in some studies using SA calcium antagonists.