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

L-Arginine, the substrate of nitric oxide (NO) synthases (SOSs), is found i n the mammalian organism at concentrations by far exceeding K-M values of t hese enzymes. Therefore, additional L-arginine should not enhance NO format ion. In vivo, however, increasing L-arginine concentration in plasma has be en shown repeatedly to increase NO production. This phenomenon has been nam ed the L-arginine parades; it has found no satisfactory explanation so far, In the present work, evidence for the hypothesis that the endogenous NOS i nhibitors methylarginines, asymmetric dimethylarginine being the most power ful (IC50 1.5 mu M), are responsible for the L-arginine parades is presente d. (C) 2000 Federation of European Biochemical Societies, Published by Else vier Science B.V. All rights reserved.