Endogenous nitric oxide synthase inhibitors are responsible for the L-arginine paradox

L-Arginine, the substrate of nitric oxide (NO) synthases (SOSs), is found in the mammalian organism at concentrations by far exceeding K-M values of these enzymes. Therefore, additional L-arginine should not enhance NO formation. In vivo, however, increasing L-arginine concentration in plasma has been shown repeatedly to increase NO production. This phenomenon has been named the L-arginine parades; it has found no satisfactory explanation so far, In the present work, evidence for the hypothesis that the endogenous NOS inhibitors methylarginines, asymmetric dimethylarginine being the most powerful (IC50 1.5 mu M), are responsible for the L-arginine parades is presented. (C) 2000 Federation of European Biochemical Societies, Published by Elsevier Science B.V. All rights reserved.