l-Arginine “Paradox” in Coronary Atherosclerosis
To the Editor:
Miner et al1 in a recent work used the steady-state 15N2-arginine 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 d- or 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.”
Miner SE, Al-Hesayen A, Kelly S, Benson T, Thiessen JJ, Young VR, Parker JD. l-arginine transport in the human coronary and peripheral circulation. Circulation. 2004; 109: 1278–1283.
Tousoulis D, Tentolouris C, Crake T, Katsimaglis G, Stefanadis C, Toutouzas P, Davies GJ. Effects of l- and d-arginine on the basal tone of human diseased coronary arteries and their responses to substance P. Heart. 1999; 81: 505–511.
Tousoulis D, Davies GJ, Tentolouris C, Goumas G, Stefanadis C, Toutouzas P. Vasomotor effects of l- and d-arginine in stenotic atheromatous coronary plaque. Heart. 2001; 86: 296–301.