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

Abstract

A deletion/insertion (D/I) polymorphism within the ACE gene may increase the risk of cardiovascular eventsthrough still unknown mechanisms. The latter 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-moderate 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-dependent vasodilator acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 μg · 100 mL-1 · min-1) in 142 subjects: 103 mild-to-moderate uncomplicated primary hypertensives (49.3±9.1 years old. 152±11/99±5 mm Hg) and 39 normotensives (44.6±15.3 years old. 122±12/78±6 mm Hg). We also assessed the endothelium-independent vasodilatation in the forearm, as blood flow response to 3 incrementally increasing doses of sodium nitroprusside (1. 2, and 4 μg · 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 primary hypertensives and normotensives. A significant blunting of endothelium-dependent vasodilatation in primary hypertensive patients compared with normotensive subjects (P<0.001) was found. No effect of the DI genotype on endothelium-dependent and -independent vasodilatation was detected. Thus, these results obtained in a relatively large population do not support the contention that the D allele is associated with a blunting of either stimulated endothelial NO or donated NO responses in both mild-to-moderate primary, hypertensive patients and normotensive subjects.