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CLINICAL STUDIES

Effects of oral L-arginine on endothelium-dependent vasodilation and markers of inflammation in healthy postmenopausal women

Arnon Blum, MD^*, Londa Hathaway, RN^*, Rita Mincemoyer, RN^*, William H. Schenke, BA^*, Martha Kirby, BA, Gyorgy Csako, MD, Myron A. Waclawiw, PhD, Julio A. Panza, MD, FACC^* and Richard O. Cannon, III, MD, FACC^*

^* Cardiology Branch, National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA
Hematology Branch Branches, National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA
Office of Biostatistics Research, National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA
Clinical Pathology Department, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA

Manuscript received January 20, 1999; revised manuscript received September 3, 1999, accepted October 21, 1999.

Reprint requests and correspondence: Dr. Richard O. Cannon, National Institutes of Health, Building 10, Room 7B15, 10 Center Drive MSC-1650, Bethesda, Maryland 20892-1650
cannonr{at}nih.gov

OBJECTIVES

We examined whether oral administration of L-arginine, the substrate for nitric oxide (NO) synthesis, increases NO bioactivity in healthy postmenopausal women.

BACKGROUND

Nitric oxide may protect arteries against atherosclerosis, as suggested by experimental studies in animals. Estrogen therapy, which has been shown to increase NO bioactivity in the vasculature of healthy postmenopausal women, is not acceptable for long-term use by many women.

METHODS

In a randomized, double-blind, crossover study, 10 postmenopausal women without additional risk factors for atherosclerosis received L-arginine 9 g or placebo daily for one month, with treatment periods separated by one month. Nitric oxide levels in serum (as an index of endothelial NO release), brachial artery endothelium-dependent dilator responses to hyperemia by ultrasonography (as an index of vascular NO bioactivity) and markers of inflammation in blood that are inhibited by NO in cell culture experiments were measured at the end of each treatment period.

RESULTS

L-arginine levels in plasma were increased in all women during L-arginine treatment compared with placebo (136.8 ± 63.1 vs. 75.2 ± 16.2 µmol/liter, p = 0.009). However, there was no change in serum nitrogen oxide levels (42.1 ± 24.5 vs. 39.1 ± 16.6 µmol/liter, p = 0.61), nor was there an effect of L-arginine on flow-mediated dilation during hyperemia (3.8 ± 3.0% vs. 4.9 ± 4.8%, p = 0.53) compared with placebo. Our study had sufficient power (ß = 0.80) to detect a true absolute treatment difference in flow-mediated brachial artery dilation of 1.7% or larger as statistically significant at alpha = 0.05. There was no effect of L-arginine on serum levels of soluble cell adhesion molecules compared with placebo: E-selectin (50.6 ± 14.8 vs. 52.1 ± 17.0 ng/ml, p = 0.45), intercellular adhesion molecule-1 (230 ± 51 vs. 230 ± 52 ng/ml, p = 0.97) and vascular cell adhesion molecule-1 (456 ± 62 vs. 469 ± 91 ng/ml, p = 0.53).

CONCLUSIONS

Oral administration of L-arginine may not augment endothelial NO synthesis and release in postmenopausal women and is thus unlikely to be of general benefit to healthy postmenopausal women in protection from the development of atherosclerosis.

Abbreviations and Acronyms   ADMA = asymmetric dimethylarginine   CRP = C-reactive protein   FITC = fluorescein isothiocyanate   ICAM-1 = intercellular adhesion molecule-1   L-NMMA = NG-monomethyl-L-arginine   NO = nitric oxide   NOS = nitric oxide synthase   VCAM-1 = vascular cell adhesion molecule-1

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