ACE genotype and endothelium-dependent vasodilation of conduit arteries and forearm microcirculation in humans

The ACE gene is a candidate gene for cardiovascular disease. Endothelial dy sfunction is considered an intermediate phenotype in the pathogenesis of hy pertension and atherosclerosis. We evaluated the role of ACE gene polymorph ism in endothelial function of young healthy humans. We assessed ACE genoty pe (deletion [D]/insertion [I] polymorphism) in 92 young healthy individual s. In 88 of them, endothelium-dependent (flow-mediated) vasodilation and en dothelium-independent (nitroglycerin-induced) vasodilation were measured in the common femoral artery and in the brachial (n=84) artery by echo Dopple r technique. In 35 subjects, we also applied the forearm perfusion techniqu e to quantify the responses of the forearm vascular bed to 3 increasing dos es of 2 endothelium-dependent vasodilators (acetylcholine and bradykinin) a nd 1 endothelium-independent vasodilator (sodium nitroprusside). The D alle le of the ACE gene was associated with a significant blunting (Delta approx imate to 26%) of endothelium-dependent vasodilation in the femoral artery ( P=0.02) but not in the brachial artery (P=0.55) or in the forearm microcirc ulation (P=0.70 to 0.80). Endothelium-independent vasodilation was unaffect ed by the ACE genotype. In young healthy humans, the D allele of the ACE ge ne is associated with selective endothelial dysfunction of the femoral arte ry. It remains to be determined whether this association discloses a causal role in vascular, particularly peripheral artery, disease.