Modification of striatal arginine and citrulline metabolism by nitric oxide synthase inhibitors

The effects of N^G-substituted L-arginine (ARG) analogues on striatal ARG and citrulline (CIT) levels were investigated using in vivo microdialysis technique. A microdialysis probe was implanted into the striatum of anaesthetized Sprague-Dawley rats. Direct intrastriatal perfusion with 1 mM N^G-nitro-L-arginine methyl ester (n = 8) increased striatal ARG release and decreased CIT release, suggesting suppressed NO synthase activity in the tissue. On the other hand, 1 mM N^G-monomethyl-L-argi-nine (L-NMMA) (n = 6) evoked a persistent increase in both ARG and CIT. Considering that 4-320 μM L-ARG (n = 8) failed to increase CIT formation, CIT seems to be synthesized in the striatal tissue from L-NMMA by the enzyme that has been demonstrated in the kidney and aortic endothelium (N^G, N^G-dimethylarginine dimethyl-aminohydrolase).