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Human Nutrition and Metabolism

Oral L-Arginine Improves Hemodynamic Responses to Stress and Reduces Plasma Homocysteine in Hypercholesterolemic Men^1,2

Sheila G. West^*,3, Andrea Likos-Krick^*, Peter Brown and François Mariotti^**

^* Department of Biobehavioral Health at Pennsylvania State University, University Park, PA 16802; Kraft Foods, Inc., Glenview, IL 60025; and ^** UMR INRA/INAPG Physiologie de la Nutrition et du Comportement Alimentaire, Institut National Agronomique Paris-Grignon, France

³To whom correspondence should be addressed. E-mail: sgw2{at}psu.edu.

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 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 umol/L) (P 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.

KEY WORDS: • L-arginine • peripheral resistance • hemodynamic • homocysteine • acute stress

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