Oral L-Arginine Improves Hemodynamic Responses to Stress and Reduces Plasma Homocysteine in Hypercholesterolemic Men

When administered intravenously, L-arginine substantially reduces blood pressure (BP) and peripheral vascular resistance in healthy adults and in patients with vascular disease. Oral L-arginine has been shown to improve endothelial function; however, it is not clear whether oral administration has significant effects on systemic hemodynamics. In a randomized, placebo-controlled, crossover study we tested whether oral L-arginine (12 g/d for 3 wk) affected hemodynamics, glucose, insulin, or C-reactive protein in 16 middle-age men with hypercholesterolemia. After each treatment, hemodynamic variables were measured at rest and during 2 standardized stressor tasks (a simulated public-speaking task and the cold pressor). Regardless of treatment, the stressor tasks increased BP and heart rate (P < or = 0.02). Relative to placebo, L-arginine changed cardiac output (-0.4 L/m), diastolic BP (-1.9 mm Hg), pre-ejection period (+3.4 ms), and plasma homocysteine (-2.0 micromol/L) (P < or = 0.03). The change in plasma L-arginine was inversely correlated with the change in plasma homocysteine (r = -0.57, P = 0.03). Contrary to the results of previous studies of L-arginine administered intravenously, oral administration did not affect total peripheral resistance or plasma insulin. Oral L-arginine also did not affect plasma glucose, C-reactive protein, or lipids. This pattern of findings is consistent with the hypothesis that oral L-arginine reduces BP. This study is the first to describe a hemodynamic mechanism for the hypotensive effect of oral L-arginine and the first to show substantial reductions in homocysteine with oral administration.