Angiotensin-Converting Enzyme Gene Polymorphism Is Associated With Endothelium-Dependent Vasodilation in Never Treated Hypertensive Patients

Abstract

Abstract —The response of the forearm vasculature to acetylcholine (7.5, 15, and 30 μg/min, each for 5 minutes) and sodium nitroprusside (0.8, 1.6, and 3.2 μg/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 μg/min), forearm blood flow was 13.9±6.3 mL · 100 mL tissue −1 · min −1 in hypertensives versus 27.1±9.7 mL · 100 mL tissue −1 · 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 · 100 mL tissue −1 · 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.