(Circulation. 2000;101:2160.)
© 2000 American Heart Association, Inc.
Clinical Investigation and Reports |
Oral L-Arginine in Patients With Coronary Artery Disease on Medical Management
From the Cardiology (A.B., L.H., R.M., W.H.S., J.A.P., R.O.C.) and Hematology (M.K.) Branches and the Office of Biostatistics Research (M.A.W.), National Heart, Lung, and Blood Institute; and the Clinical Pathology Department (G.C.), Clinical Center, National Institutes of Health, Bethesda, Md.
Correspondence to Richard O. Cannon III, MD, National Institutes of Health, Bldg 10, Room 7B15, 10 Center Dr, MSC 1650, Bethesda, MD 20892-1650. E-mail cannonr{at}nih.gov
Background—Vascular nitric oxide (NO) bioavailability is reduced in patients with coronary artery disease (CAD). We investigated whether oral L-arginine, the substrate for NO synthesis, improves homeostatic functions of the vascular endothelium in patients maintained on appropriate medical therapy and thus might be useful as adjunctive therapy.
Methods and Results—Thirty CAD patients (29 men; age, 67±8 years) on appropriate medical management were randomly assigned to L-arginine (9 g) or placebo daily for 1 month, with crossover to the alternate therapy after 1 month off therapy, in a double-blind study. Nitrogen oxides in serum (as an index of endothelial NO release), flow-mediated brachial artery dilation (as an index of vascular NO bioactivity), and serum cell adhesion molecules (as an index of NO-regulated markers of inflammation) were measured at the end of each treatment period. L-Arginine significantly increased arginine levels in plasma (130±53 versus 70±17 µmol/L, P<0.001) compared with placebo. However, there was no effect of L-arginine on nitrogen oxides (19.3±7.9 versus 18.6±6.7 µmol/L, P=0.546), on flow-mediated dilation of the brachial artery (11.9±6.3% versus 11.4±7.9%, P=0.742), or on the cell adhesion molecules E-selectin (47.8±15.2 versus 47.2±14.4 ng/mL, P=0.601), intercellular adhesion molecule-1 (250±57 versus 249±57 ng/mL, P=0.862), and vascular cell adhesion molecule-1 (567±124 versus 574±135 ng/mL, P=0.473).
Conclusions—Oral L-arginine therapy does not improve NO bioavailability in CAD patients on appropriate medical management and thus may not benefit this group of patients.
Key Words: atherosclerosis • coronary disease • endothelium • nitric oxide
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