Effect of a selective inducible nitric oxide synthase inhibitor on intraocular nitric oxide production in endotoxin-induced uveitis rabbits: in vivo intraocular microdialysis study

Inducible nitric oxide (NO) synthase (iNOS) is believed to contribute to the pathogenesis of endotoxin-induced uveitis (EIU). In the present study, we investigated the inhibitory effects of N-G-nitro-L-arginine methyl ester (L-NAME), a non-selective NOS inhibitor, and S,S'-1,4-phenylene-bis(1,2-ethanediyl)bis-isothiourea (PBITU), a potent and selective iNOS inhibitor, on intraocular NO production in EIU rabbits using an in vivo intraocular microdialysis technique. The flare level in the anterior chamber increased from 1 h after the injection of 100 mug/kg lipopolysaccharide (LPS), and continued to increase for 24 h. Aqueous humor protein concentrations were significantly increased at 24 h after LPS-injection. These changes were significantly reduced by L-NAME (10 mg/kg) and PBITU (1 mg/kg), but not by D-NAME (10 mg/kg). The increase in NO2- and NO3- levels in the dialysate induced by LPS was significantly inhibited by L-NAME (10 mg/kg) and PBITU (1 mg/kg), but not by D-NAME (10 mg/kg). These results suggest that activation of iNOS may play a key role in the development of EIU, and selective inhibitors of iNOS may have therapeutic applications in the treatment of EIU. (C) 2003 Elsevier Science Ltd. All rights reserved.