Different phenotypes of the NAT2 gene influences hydralazine antihypertensive response in patients with resistant hypertension.
OBJECTIVE
Hydralazine, a vasodilator used in resistant hypertension (RH) treatment is metabolized by an acetylation reaction mediated by N-acetyltransferase 2, the activity of which depends on NAT2 polymorphisms. Our aim was to evaluate whether different acetylation phenotypes influenced the antihypertensive effect of hydralazine in patients with RH.


METHODS
DNA samples from 169 RH patients using hydralazine were genotyped by sequencing the NAT2 coding region, and acetylation phenotypes were defined.


RESULTS
Sixty-five patients (38.5%) were intermediate, 60 (35.5%) slow and 21 (12.4%) fast acetylators. Twenty-three (13.6%) patients were indeterminate. Upon association analysis, only slow acetylators had significant blood pressure reductions after hydralazine use, with mean 24-h systolic and diastolic blood pressure reductions of 9.2 and 5.5 mmHg. Four patients presented hydralazine adverse effects resulting in drug withdrawal, three of them were slow acetylators.


CONCLUSIONS
The slow acetylation phenotype, determined by polymorphisms within NAT2, influenced both the antihypertensive and adverse effects of hydralazine in RH.
Laboratory of Molecular Biology Applied to Mycobacteria - Oswaldo Cruz Institute - Fiocruz, Av. Brazil 4365, CEP: 21040-360, Manguinhos, Rio de Janeiro, Brazil.
Lizania Borges
LB
Spinasse
Adalberto Rezende
AR
Santos
Philip Noel
PN
Suffys
Elizabeth Silaid
ES
Muxfeldt
Gil Fernando
GF
Salles
D000107:Acetylation / Q000187:drug effects; D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006801:Humans; D006830:Hydralazine / Q000008:administration & dosage*; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic
D000959:Antihypertensive Agents; D006830:Hydralazine; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human