Reversal of hypercholesterolemia-induced endothelial dysfunction by L-arginine.

Abstract

H ypercholesterolemia impairs endothelial function (manifested as an attenuation of endothelium-dependent relaxation) prior to the formation of atherosclerotic lesions. Endothelial dysfunction in return can evoke abnormal interactions between the vascular wall and blood cells (neutrophils, monocytes, and platelets) and promote expression of mitogens, which contribute to the development of atherosclerosis.1 Thus, early treatment of endothelial dysfunction may prevent the later consequences of this abnormality, including atherosclerosis. In a paper published in this issue of Circulation, Cooke et a12 report that infusion of L-arginine (the proposed precursor of endotheliumderived relaxing factor [EDRF]) to hypercholesterolemic rabbits normalizes endothelium-dependent relaxation. This finding suggests that increasing the synthesis of EDRF may be of benefit in the reversal of endothelial dysfunction caused by hypercholesterolemia, and could be a novel approach to prevent the development of atherosclerotic lesions.