[Pathogenetic aspects of the L-arginine-NO metabolic pathway in arteriosclerosis and possible therapeutic aspects].

L-arginine is the physiological precursor of nitric oxide (NO) which is formed in endothelial cells by the activity of the constitutive NO synthase isoenzyme. NO is tonically released from the endothelium, thus maintaining an active vasodilator tone and inhibiting platelet aggregation, leukocyte adhesion, and vascular smooth muscle cell proliferation. In experimental hypercholesterolemia and atherosclerosis as well as in hypercholesterolemic patients, NO-mediated responses have been shown to be impaired. Whether decreased formation and/or enhanced oxidative inactivation are involved in this process, is still unclear. Chronic dietary administration of L-arginine has been shown to exert anti-atherosclerotic effects in hypercholesterolemic rabbits. Intravenous infusion of L-arginine induces NO-dependent peripheral vasodilatation and inhibits platelet aggregation in healthy humans as well as in patients with severe limb ischemia and generalized atherosclerosis. Whether L-arginine may induce therapeutic effects in peripheral vascular disease, still remains unclear.