Hydrochlorothiazide efficacy and polymorphisms in ACE, ADD1 and GNB3 in healthy, male volunteers

The antihypertensive effect of thiazide diuretics has recently been associated with genetic variation in the angiotensin I-converting enzyme (ACE), alpha-adducin (ADD1) and the G protein subunit beta3 (GNB3). Analysis of short-term diuretic effects may provide insight into the mechanisms behind thes...

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Bibliographic Details
Published in:European journal of clinical pharmacology 2006-03, Vol.62 (3), p.195-201
Main Authors: VORMFELDE, Stefan Viktor, SEHRT, Daniel, BOLTE, Daniela, PAHL, Susanne, TZVETKOV, Miaden, BROCKMOLLER, Jürgen
Format: Article
Language:English
Subjects:
Adolescent
Adult
Analysis of Variance
Antihypertensive Agents - pharmacology
Antihypertensive Agents - urine
Biological and medical sciences
Calcium - urine
Calmodulin-Binding Proteins - genetics
Chlorides - urine
Diuretics - pharmacology
Diuretics - urine
Dose-Response Relationship, Drug
Genotype
Heart Rate - drug effects
Heterotrimeric GTP-Binding Proteins - genetics
Humans
Hydrochlorothiazide - pharmacology
Hydrochlorothiazide - urine
Male
Medical sciences
Middle Aged
Peptidyl-Dipeptidase A - genetics
Pharmacology. Drug treatments
Polymorphism, Genetic - genetics
Potassium - urine
Single-Blind Method
Sodium - urine
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Summary:The antihypertensive effect of thiazide diuretics has recently been associated with genetic variation in the angiotensin I-converting enzyme (ACE), alpha-adducin (ADD1) and the G protein subunit beta3 (GNB3). Analysis of short-term diuretic effects may provide insight into the mechanisms behind these findings. A total of 103 male volunteers took 25 and 100 mg hydrochlorothiazide (HCT) after a placebo day, each. We measured volume, sodium, chloride, potassium, calcium excretion, blood pressure and heart rate. Excretion and cardiovascular parameters were highly constant between the 2 placebo days. The resting heart rate was 2-3 beats/minute (bpm) higher per ACE insertion allele on all 4 study days. The HCT-induced excretion of sodium, chloride and volume was independent of the genotypes. The additional potassium excretion induced by 100 mg HCT was 44+/-21, 33+/-27 and 16+/-26 mmol (mean+/-SD, p
ISSN:0031-6970
1432-1041
DOI:10.1007/s00228-005-0081-z