POTENT INHIBITION OF HUMAN NEURONAL NITRIC-OXIDE SYNTHASE BY N-G-NITRO-L-ARGININE METHYL-ESTER RESULTS FROM CONTAMINATING N-G-NITRO-L-ARGININE

N-G-Nitro-L-arginine methyl ester (L-NAME), inhibits the three isozyme s of nitric oxide synthase (NOS) in vitro and in vivo.. The mechanism of NOS inhibition by L-NAME is uncertain. L-NAME was a time-dependent inhibitor of neuronal NOS (nNOS). Concommitantly, L-NAME was hydrolyze d, non-enzymatically, to N-G-Nitro-L-arginine (L-NA) during the enzyme assay. The time-dependent inhibition of nNOS by L-NAME was the result of this time-dependent formation of L-NA. Furthermore, N-G-Nitro-L-ar ginine methyl amide, which is an isosteric analogue of L-NAME that is much less susceptible to hydrolysis, was a rapidly reversible weak inh ibitor of NOS. These data suggested that L-NAME itself was a weak and rapidly reversible inhibitor of nNOS. Most of the inhibition of nNOS b y a solution of L-NAME is the result of the formation of L-NA. L-NAME was a substrate for porcine liver esterase.