ACE D/I gene polymorphism does not predict endothelial dysfunction in the human peripheral microcirculation

A deletion/insertion (D/I) polymorphism within the ACE gene may increase the risk of cardiovascular events through 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 mg z 100 mL21 z min21) in 142 subjects: 103 mild-to-moderate uncomplicated primary hypertensives (49.369.1 years old, 152611/9965 mm Hg) and 39 normotensives (44.6615.3 years old, 122612/7866 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 mg z 100 mL21 z min21). The overall genotype distribution was II, n510; ID, n570; and DD, n562. 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.