Effect of enalaprilat on nitric oxide activity in coronary artery disease

Atherosclerosis is associated with vascular endothelial dysfunction and red uced nitric oxide (NO) activity. Enhancement of NO activity may have an ant iatherogenic action. This study was performed to determine whether angioten sin-converting enzyme (ACE) inhibition improves peripheral vascular NO acti vity in patients with atherosclerosis. In the femoral circulation of 43 pat ients with atherosclerosis and 10 controls, we studied endothelium-dependen t vasodilation with bradykinin and acetylcholine, and endothelium-independe nt vasodilation with sodium nitroprusside before and after enalaprilat, In 22 patients, we repeated these infusions in the presence of L-N-G monomethy l arginine (L-NMMA). Doppler-femoral artery flow velocity was measured. Bef ore ACE inhibition, acetylcholine responses were depressed in patients with atherosclerosis compared with controls (p = 0.03). Enalaprilat did not alt er femoral vascular tone at rest or vasodilation with sodium nitroprusside, but potentiated bradykinin-mediated vasodilation in patients (p <0.001) an d controls (p = 0.02). Acetylcholine-mediated vasodilation was augmented on ly in patients (p <0.001), but not in control subjects. L-NMMA inhibited th e potentiation by enalaprilat of acetylcholine and bradykinin responses. Th is study demonstrates that ACE inhibition selectively improves endothelial dysfunction in human atherosclerosis by enhancing NO activity. The antithro mbotic and antiproliferative effects of NO may reduce adverse manifestation s related to atherosclerosis during long-term therapy, (C) 1999 by Excerpta Medico, Inc.