Effect of enalaprilat on nitric oxide activity in coronary artery disease.
Atherosclerosis is associated with vascular endothelial dysfunction and reduced nitric oxide (NO) activity. Enhancement of NO activity may have an antiatherogenic action. This study was performed to determine whether angiotensin-converting enzyme (ACE) inhibition improves peripheral vascular NO activity in patients with atherosclerosis. In the femoral circulation of 43 patients with atherosclerosis and 10 controls, we studied endothelium-dependent vasodilation with bradykinin and acetylcholine, and endothelium-independent vasodilation with sodium nitroprusside before and after enalaprilat. In 22 patients, we repeated these infusions in the presence of L-N(G) monomethyl arginine (L-NMMA). Doppler-femoral artery flow velocity was measured. Before ACE inhibition, acetylcholine responses were depressed in patients with atherosclerosis compared with controls (p = 0.03). Enalaprilat did not alter femoral vascular tone at rest or vasodilation with sodium nitroprusside, but potentiated bradykinin-mediated vasodilation in patients (p<0.001) and controls (p = 0.02). Acetylcholine-mediated vasodilation was augmented only in patients (p<0.001), but not in control subjects. L-NMMA inhibited the potentiation by enalaprilat of acetylcholine and bradykinin responses. This study demonstrates that ACE inhibition selectively improves endothelial dysfunction in human atherosclerosis by enhancing NO activity. The antithrombotic and antiproliferative effects of NO may reduce adverse manifestations related to atherosclerosis during long-term therapy.
Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1650, USA.
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Prasad
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Husain
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Quyyumi
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000378:metabolism; D015773:Enalaprilat / Q000627:therapeutic use*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005263:Femoral Artery / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D015203:Reproducibility of Results; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000502:physiology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D015773:Enalaprilat