Effects of valsartan or amlodipine alone or in combination on plasma catecholamine levels at rest and during standing in hypertensive patients.
To compare the effects of valsartan and amlodipine alone or in combination on plasma norepinephrine (NE) at rest and standing for 10 minutes in patients with hypertension, 47 patients with a sitting diastolic blood pressure (BP) (DBP)>95 mm Hg and<110 mm Hg were randomized in a double-blind fashion to either valsartan or amlodipine. During the first 4 weeks of treatment, patients received a low dose of either valsartan (80 mg) or amlodipine (5 mg). The patients were force-titrated to the high dose of either drug (160 or 10 mg) for 4 weeks. After 8 weeks of therapy, those who still had a DBP>90 mm Hg (nonresponders) received combination therapy with the other drug, whereas patients with a DBP<90 mm Hg (responders) continued on monotherapy. Decreases in ambulatory BP and clinic systolic BP and DBP were significant (P<.05) after 8 weeks' therapy with no difference between the 2 groups. Amlodipine but not valsartan as monotherapy consistently increased NE levels at rest and enhanced NE levels during standing. Valsartan decreased basal NE in responders. Combination therapy with valsartan and amlodipine did not attenuate the rise in NE levels induced by amlodipine. This study indicates that therapy with amlodipine increases peripheral sympathetic basal tone and reactivity to standing in patients with hypertension, whereas valsartan does not. Combined therapy with amlodipine/valsartan did not attenuate the sympathetic activation induced by amlodipine. The hypotensive action of valsartan may be mediated in part by an inhibition of the sympathetic baroreflex in patients with hypertension.
de Champlain
Jacques
J
Institut de Recherches Cliniques de Montréal, Faculty of Medicine, Université de Montréal, Sacré-Coeur Hospital, Québec, Canada. jacques.de.champlain@umontreal.ca
Karas
Maria
M
Assouline
Linda
L
Nadeau
Reginald
R
LeBlanc
A Robert
AR
Dubé
Bruno
B
Larochelle
Pierre
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D017311:Amlodipine / Q000627:therapeutic use*; D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000097:blood*; D002851:Chromatography, High Pressure Liquid; D004359:Drug Therapy, Combination; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011187:Posture / Q000502:physiology*; D012146:Rest / Q000502:physiology*; D013777:Tetrazoles / Q000627:therapeutic use*; D016896:Treatment Outcome; D014633:Valine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000068756:Valsartan
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D015415:Biomarkers; D002395:Catecholamines; D013777:Tetrazoles; D017311:Amlodipine; D000068756:Valsartan; D014633:Valine