Exclusion of the ACE D/I gene polymorphism as a determinant of endothelialdysfunction

A deletion/insertion (D/I) polymorphism within the ACE gene may increase th e risk of cardiovascular events through Still unknown mechanisms. The latte r may involve increased angiotensin II-induced NO breakdown and/or reduced agonist-mediated NO release. We therefore investigated whether the D allele of the ACE gene affects endothelium-dependent vasodilatation in mild-to-mo derate primary hypertensive patients and healthy normotensive subjects. We compared in a cross-sectional study the forearm blood flow response of the 3 D/I genotypes with 5 incrementally increasing doses of the endothelium-de pendent vasodilator acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 mug . 100 m L(-1) . min(-1)) in 142 subjects: 103 mild-to-moderate uncomplicated primar y hypertensives (49.3+/-9.1 years old, 152+/-11/99+/-5 mm Hg) and 39 normot ensives (44.6+/-15.3 years old, 122+/-12/78+/-6 mm Hg). We also assessed th e endothelium-independent vasodilatation in the forearm, as blood flow resp onse to 3 incrementally increasing doses of sodium nitroprusside (1, 2, and 4 mug . 100 mL(-1) . min(-1)). The overall genotype distribution was II, n =10; ID, n=70; and DD, n=62. It did not differ significantly between primar y hypertensives and normotensives. A significant blunting of endothelium-de pendent vasodilatation in primary hypertensive patients compared with normo tensive subjects (P<0.001) was found. No effect of the DI genotype on endot helium-dependent and -independent vasodilatation was detected. Thus, these results obtained in a relatively large population do not support the conten tion that the D allele is associated with a blunting of either stimulated e ndothelial NO or donated NO responses in both mild-to-moderate primary hype rtensive patients and normotensive subjects.