Angiotensin-converting enzyme gene polymorphism is associated with endothelium-dependent vasodilation in never treated hypertensive patients.
The response of the forearm vasculature to acetylcholine (7.5, 15, and 30 microg/min, each for 5 minutes) and sodium nitroprusside (0.8, 1.6, and 3.2 microg/min, each for 5 minutes) was evaluated in 32 never-treated hypertensive outpatients (17 men and 15 women, aged 43+/-7 years) and in 24 normotensive control subjects (14 men and 10 women, aged 42+/-6 years). Drugs were infused into the brachial artery, and forearm blood flow was measured by strain-gauge plethysmography. In both hypertensive and normotensive groups, a deletion (D)/insertion (I) polymorphism in intron 16 of the angiotensin-converting enzyme (ACE) gene was determined by polymerase chain reaction. The response to acetylcholine was significantly reduced in hypertensive patients versus control subjects: at the highest dose (30 microg/min), forearm blood flow was 13.9+/-6.3 mL x 100 mL tissue(-1) x min(-1) in hypertensives versus 27.1+/-9.7 mL x 100 mL tissue(-1) x min(-1) in the controls (P<.001); similarly, vascular resistance was 10.6+/-5.6 U in hypertensive patients and 4.9+/-1.9 U in normotensive subjects. In the hypertensive group, the patients with DD genotype showed significantly less endothelium-dependent vasodilation compared with ID+II genotypes (at the highest dose of acetylcholine, forearm blood flow was 12.1+/-4.2 versus 17.0+/-4.1 mL x 100 mL tissue(-1) x min(-1)) (P<.005). The vasodilator effect of sodium nitroprusside infusions was not statistically different in DD and ID+II hypertensive patients. In conclusion, our data suggest that ACE polymorphism affects endothelium-dependent vasodilation in hypertensive patients and confirm that hypertensive patients had a blunted response to the endothelium-dependent agent acetylcholine.
Perticone
F
F
Department of Medicina Sperimentale e Clinica G. Salvatore at Catanzaro, University of Reggio Calabria, Italy. perticone@unicz.thebrain.net
Ceravolo
R
R
Maio
R
R
Ventura
G
G
Zingone
A
A
Perrotti
N
N
Mattioli
P L
PL
D000328:Adult; D000704:Analysis of Variance; D001794:Blood Pressure; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D014664:Vasodilation / Q000502:physiology*
D007703:Peptidyl-Dipeptidase A