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(Circulation. 1997;95:311-312.)
© 1997 American Heart Association, Inc.

Articles

Arginine: A New Therapy for Atherosclerosis?

John P. Cooke, MD, PhD; Philip S. Tsao, PhD

the Stanford (Calif) School of Medicine.

Correspondence to Philip S. Tsao, PhD, Division of Cardiovascular Medicine, Stanford School of Medicine, 300 Pasteur Dr, CVRB, Stanford, CA 94305-5246.

Key Words: Editorials • atherosclerosis • arginine

	Introduction

 
In this issue of Circulation, Aji et al¹ provide compelling evidence for an antiatherogenic effect of dietary arginine supplementation. To examine the effect of arginine on the progression of atherosclerosis, they used a murine model in which the LDL receptor is disrupted by homologous recombination. This results in a deficiency of functional LDL receptors much like that observed in familial hypercholesterolemia in humans. In response to a high-fat diet, these animals develop severe hypercholesterolemia, xanthoma formation, and accelerated atherosclerosis.² In this study, dietary arginine supplementation markedly reduced the development of intimal lesions. Furthermore, xanthoma formation was abolished. These effects of arginine were probably due to its conversion to NO, because they were abrogated by coadministration of nitro-L-arginine, an antagonist of NOS.

This article adds further weight to the accumulating evidence that dietary supplementation of arginine inhibits atherogenesis. The present investigation also supports the hypothesis that arginine exerts its effects by enhancing the synthesis of NO.

Arginine is a semiessential amino acid that, among other functions, also serves as the substrate for the enzyme NOS, which converts arginine to citrulline and NO.³ Normally, arginine is not rate-limiting in this reaction; the K_m for NOS is in the micromolar range,⁴ whereas intracellular levels of arginine are in the millimolar range. Under certain conditions, however, arginine administration can enhance the synthesis of NO. In hypercholesterolemic rabbits and humans, endothelium-dependent vasodilation due to NO is impaired; administration of arginine restores endothelium-dependent vasodilation.^{5 6 7 8} Using chemiluminescent techniques, we have shown that this effect of . . . [Full Text of this Article]

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