Does Blockade of the Renin Angiotensin System Affect Sympathetic and Blood Pressure Responses to Amlodipine in Young Hypertensive Patients?

Background Angiotensin II-mediated increases in sympathetic activity may contribute to smaller blood-pressure decreases in response to dihydropyridines in young versus older hypertensive patients. We evaluated whether quinapril unmasks angiotensin II-dependent sympathetic activity on amlodipine. Methods In this double-blind, randomized, clinical trial, young mild hypertensives were randomized to quinapril for 1 week (study 1), followed by quinapril + amlodipine for 6 weeks (study 2), followed by amlodipine + placebo for 6 weeks (study 3), or else were randomized to placebo for 1 week (study 1), followed by placebo + amlodipine for 6 weeks (study 2), followed by amlodipine + quinapril for 6 weeks (study 3). Muscle sympathetic nerve activity (MSNA) and plasma hormones were analyzed at the end of each treatment period. Twenty-one subjects completed this study. Results Quinapril alone decreased BP by 8 ± 3/6 ± 3 (mean ± SD) mm Hg, and amlodipine alone decreased BP by 6 ± 3/4 ± 2 (mean ± SD). Quinapril combined with amlodipine caused a drop of 13 ± 3/13 ± 3 (mean ± SD) mm Hg in one group, and 14 ± 3/14 ± 2 (mean ± SD) mm Hg in the second group. Six weeks after discontinuation of quinapril, amlodipine alone caused no change (0 ± 3/−2 ± 3) (mean ± SD). The MSNA decreased by 3 bursts/100 heartbeats at visits 2 v 1 and 3 v 2 (P = .02 for time effect), regardless of treatment. Angiotensin II showed small increases with each visit in the first group, and small decreases in the second group (P = .02 for treatment effect). Conclusions It appears that amlodipine does not activate the renin-angiotensin system to counteract its BP-lowering effect in young hypertensives. Similarly, no angiotensin II-dependent component in MSNA appears to be present at baseline or to be induced by amlodipine.