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

OBJECTIVES We examined whether oral administration of L-arginine, the subst rate for nitric oxide (NO) synthesis, increases NO bioactivity in healthy p ostmenopausal women. BACKGROUND Nitric oxide may protect arteries against atherosclerosis, as su ggested by experimental studies in animals. Estrogen therapy, which has bee n shown to increase NO bioactivity in the vasculature of healthy postmenopa usal women, is not acceptable for long-term use by many women. METHODS In a randomized, double-blind, crossover study, 10 postmenopausal w omen without additional risk factors for atherosclerosis received L-arginin e 9 g or placebo daily for one month, with treatment periods separated by o ne month. Nitric oxide levels in serum (as an index of endothelial NO relea se), brachial artery endothelium-dependent dilator responses to hyperemia b y ultrasonography (as an index of vascular NO bioactivity) and markers of i nflammation in blood that are inhibited by NO in cell culture experiments w ere measured at the end of each treatment period. RESULTS L-arginine levels in plasma were increased in all women during L-ar ginine treatment compared with placebo (136.8 +/- 63.1 vs. 75.2 +/- 16.2 mu mol/liter, p = 0.009). However, there was no change in serum nitrogen oxid e levels (42.1 +/- 24.5 vs. 39.1 +/- 16.6 mu mol/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 ha d sufficient power (beta = 0.80) to detect a true absolute treatment differ ence in flow-mediated brachial artery dilation of 1.7% or larger as statist ically significant at alpha = 0.05. There was no effect of L-arginine on se rum levels of soluble cell adhesion molecules compared with placebo: E-sele ctin (50.6 +/- 14.8 vs. 52.1 +/- 17.0 ng/ml, p = 0.45), intercellular adhes ion molecule-1 (230 +/- 51 vs. 230 +/- 52 ng/ml, p = 0.97) and vascular cel l adhesion molecule-1 (456 +/- 62 us. 469 +/- 91 ng/ml, p = 0.53). CONCLUSIONS Oral administration oil-arginine may not augment endothelial NO synthesis and release in postmenopausal women and is thus unlikely to be o f general benefit to healthy postmenopausal women in protection from the de velopment of atherosclerosis. (J Am Coll Cardiol 2000;35:271-6) (C) 2000 by the American College of Cardiology.