ANGIOTENSIN-CONVERTING ENZYME GENE POLYMORPHISM IS ASSOCIATED WITH ENDOTHELIUM-DEPENDENT VASODILATION IN NEVER TREATED HYPERTENSIVE PATIENTS

The response of the forearm vasculature to acetylcholine (7.5, 15, and 30 mu g/min, each for 5 minutes) and sodium nitroprusside (0.8, 1.6, and 3.2 mu g/min, each for 5 minutes) was evaluated in 32 never-treate d hypertensive outpatients (17 men and 15 women, aged 43+/-7 years) an d in 24 normotensive control subjects (14 men and 10 women, aged 42+/- 6 years). Drugs were infused into the brachial artery, and forearm blo od flow was measured by strain-gauge plethysmography. In both hyperten sive and normotensive groups, a deletion (D)/insertion (I) polymorphis m in intron 16 of the angiotensin-converting enzyme (ACE) gene was det ermined by polymerase chain reaction. The response to acetylcholine wa s significantly reduced in hypertensive patients versus control subjec ts: at the highest dose (30 mu g/min), forearm blood flow was 13.9+/-6 .3 mL.100 mt tissue(-1).min(-1) in hypertensives versus 27.1+/-9.7 mL. 100 mt tissue(-1).min(-1) in the controls (P<.001); similarly, vascula r 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 wit h DD genotype showed significantly less endothelium-dependent vasodila tion compared with ID+II genotypes (at the highest dose of acetylcholi ne, forearm blood flow was 12.1+/-4.2 versus 17.0+/-4.1 mL.100 mt tiss ue(-1).min(-1)) (P<.005). The vasodilator effect of sodium nitroprussi de infusions was not statistically different in DD and ID+II hypertens ive patients. In conclusion, our data suggest that ACE polymorphism af fects endothelium-dependent vasodilation in hypertensive patients and confirm that hypertensive patients had a blunted response to the endot helium-dependent agent acetylcholine.