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.
Ruzicka
Marcel
M
Hypertension Unit, Division of Cardiology, University of Ottawa Heart Institute, Ottawa, Ontario, Canada. mruzicka@ottawahospital.on.ca
Coletta
Elizabeth
E
Leenen
Frans H H
FH
D000328:Adult; D017311:Amlodipine / Q000627:therapeutic use*; D000803:Angiotensin I / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects / Q000294:innervation; D009638:Norepinephrine / Q000097:blood; D000077583:Quinapril; D012083:Renin / Q000097:blood; D013564:Sympathetic Nervous System / Q000187:drug effects*; D044005:Tetrahydroisoquinolines / Q000627:therapeutic use*
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D044005:Tetrahydroisoquinolines; D000804:Angiotensin II; D017311:Amlodipine; D000803:Angiotensin I; D012083:Renin; D000077583:Quinapril; D009638:Norepinephrine