To determine the role of the renin-angiotensin-aldosterone (RAA) system in the acute effect of calcium channel blockers, we examined the acute effect of 40 mg nicardipine in 21 essential hypertensive patients. Nine patients whose mean blood pressure (MBP) decreased more than 5% at 2 hours after 20 mg furosemide i.v. were classified as salt-sensitive (SS); the remainder as salt-resistant (SR). The percentage decrease of MBP with nicardipine was not different between the two subgroups (12.4 +/- 2.5% for SS, and 17.7 +/- 4.1% for SR). The percentage decrease of MBP correlated with the pretreatment MBP (r = 0.67, p < 0.001), but not with the basal plasma renin activity (PRA), plasma aldosterone concentration (PAC), or natriuretic response. A significant increase of heart rate was noted in SR (31.2%) but not in SS (6.5%), and was associated with a higher increase of PRA in SR (90.7%) than in SS (25.5%). A correlation between the increase of PRA and the percentage increase of heart rate was noted (r = 0.77 p < 0.001). Decrease of PAC was observed in SS but not in SR until the third hour. The 3-hour sodium excretion was slightly greater in SR than in SS (59.9 +/- 9.1 vs. 35.1 +/- 3.0 mEq; p < 0.05). In summary, the acute hypotensive effect of nicardipine is dependent upon the vascular tone regardless of the status of the RAA system. An increase in PRA by nicardipine resulting from a baroreflex mechanism may counteract the inhibitory effect of aldosterone secretion by nicardipine. The unchanged PRA in SS is due to their blunted baroreflex control of heart rate. Mechanisms other than the change in the RAA system by nicardipine may account for the acute natriuretic effect.