Amino acids, arginase and nitric oxide in vascular health.

1. Nitric oxide (NO) plays a fundamental role in the vasculature because of its diverse influence in vascular protection, including its well-reported antiproliferative, anti-inflammatory, antithrombotic and vasodilator effects. In many vascular disease states, NO production is reduced as a result of endothelial dysfunction, in part caused by a decrease in substrate (L-arginine) availability. 2. The role of L-arginine and other amino acids important in nitrogen balance has been re-examined in the context of their effects on vascular health. The metabolism of L-arginine is complex because it is involved in a plethora of other pathways, such as urea, creatine and agmatine production. L-Arginine supplementation in patients with vascular disease is well reported to benefit patients therapeutically because of its effect on both NO-dependent and -independent mechanisms. 3. L-Arginine availability depends on the flux of other amino acids in the body, including L-glutamine, L-glutamate, L-ornithine, L-citrulline and L-lysine. The role of L-methionine and homocystine and their effect on NO also play an influential role in the body. 4. Recent data suggest that the key enzyme involved in the L-arginine-urea cycle, arginase, is coexpressed in NO-producing cells in the vasculature. In the present review, we examine the potential role of arginase as a therapeutic target for vascular health.