L-arginine "paradox" in coronary atherosclerosis.

To the Editor: Miner et al1 in a recent work used the steady-state N2arginine to examine the transorgan L-arginine gradients in the peripheral and coronary circulation. They found that during acetylcholine infusion a significant gradient was detected, indicating that the stimulation of NOS induces arginine transport. A body of evidence suggests that L-arginine supplementation improves endothelium-dependent vasomotor responses. This response to elevated extracellular L-arginine despite high intracellular L-arginine concentration has been called the “arginine paradox.” We2–4 have examined the acute effects of intracoronary infusion of L-arginine in patients with stable angina and advanced atherosclerosis. L-Arginine administration was associated with significant dilatation of stenoses of proximal segments of both “normal” and diseased arteries, and of distal segments of diseased arteries (P 0.01). No significant changes were associated with D-arginine administration. The magnitude of dilatation of stenoses and all segments of both “normal” and diseased coronaries was greater after L-arginine (P 0.05), but not after D-arginine and substance P infusion, than it was after saline and substance P infusion. Administration of Dor L-arginine did not change the magnitude of substance P–induced dilatation.2 The dilation of proximal and distal segments in response to low-dose L-arginine was greater in patients with a serum cholesterol level 200 mg/dL than in patients with a level 200 mg/dL, whereas the response was the same in smokers and nonsmokers.3 During L-arginine infusion a larger proportion of complex stenoses than smooth stenoses dilated by 10%, and the magnitude of dilatation was greater at the site of complex stenoses (P 0.05).4 Our intracoronary studies indicate that acute intracoronary L-arginine supplementation may improve endothelium-dependent vasodilation in coronary arteries in patients with coronary artery disease and support the theory of “arginine paradox.”