Methylene blue inhibits hippocampal nitric oxide synthase activity in vivo

The aim of the present study was to investigate the effect of methylene blu e, a guanylate cyclase inhibitor, on the hippocampal nitric oxide synthase activity in vivo. We used a microdialysis-based technique of measuring conv ersion of [H-3]L-arginine to [H-3]L-citrulline in freely moving rats. The a dministration of methylene blue (0.1 and 1 mM) via the microdialysis probe caused a dose-dependent decrease in [H-3]L-citrulline efflux comparable wit h the effect of unselective NOS inhibitor N-G-nitro-L-arginine (2 mM). We c onclude that methylene blue inhibits brain NOS activity in vivo and thus in terferes with NO-cGMP cascade in different levels. (C) 1999 Elsevier Scienc e B.V. All rights reserved.