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Endothelium plays a primary role in local regulation of vascular activity by synthesis and release of vasoactive substances, including the endothelium-derived relaxing factor, now identified with nitric oxide (NO), a labile substance derived from l-arginine. From its discovery [1, 2], NO has been recognized as a major intercellular, and perhaps intracellular, mediator [1, 2]. NO has potent biological properties as a vasoactive, platelet-regulatory, neurotransmitter and also cytotoxic agent [3]. Disorders of the endothelial NO synthase pathway might play a role in cardiovascular disorders including systemic and pulmonary hypertension [4–8], hypercholesterolaemia [9]and atherosclerosis [10, 11]although it is still unclear whether the decrease in endothelium-dependent vasorelaxation observed in hyperlipidaemia results from an increase in NO inactivation [12, 13]or a decreased formation of this compound [14, 15].Investigators used arginine, the substrate of NO synthase, and antagonists of NO synthase as pharmacological means to manipulate the pathway. Only recently the idea emerged that arginine is not only a substrate for the enzyme which converts it to NO and citrulline but also a nutrient whose intake is highly variable among individuals and among populations. Although arginine was recently presented as a new possible pharmacological agent for atherosclerosis [16], the hypothesis that chronic high or low intake of arginine may play a role in coronary heart disease (CHD) has not been documented yet.In the present issue of Cardiovascular Research , Bode-Boger et al. report that dietary arginine interferes with the metabolism of eicosanoids in a rabbit model of hypercholesterolaemia [17]. The cholesterol-induced increase of thromboxane A2, a potent vasoconstrictor and activator of platelet function derived from arachidonic acid, was significantly attenuated by arginine, the formation of atherosclerotic-type lesions and platelet function were partly inhibited and the vasoconstrictor effect of serotonin on isolated aortic … * Tel.: +33 (4) 77828300; fax: +33 (4) 77828447; e-mail: lorgeril@univ-st-etienne.fr

Dietary arginine and the prevention of cardiovascular diseases