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 1h after the injection of 100 micro g/kg lipopolysaccharide (LPS), and continued to increase for 24h. Aqueous humor protein concentrations were significantly increased at 24h after LPS-injection. These changes were significantly reduced by L-NAME (10mg/kg) and PBITU (1mg/kg), but not by D-NAME (10mg/kg). The increase in NO(2)(-) and NO(3)(-) levels in the dialysate induced by LPS was significantly inhibited by L-NAME (10mg/kg) and PBITU (1mg/kg), but not by D-NAME (10mg/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.
Department of Ophthalmology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan.
Kentaroh
K
Kamata
Masato
M
Inazu
Hiroshi
H
Takeda
Hiroshi
H
Goto
Teruhiko
T
Matsumiya
Masahiko
M
Usui
D000818:Animals; D001082:Aqueous Humor / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D008070:Lipopolysaccharides; D008297:Male; D017551:Microdialysis / Q000379:methods*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009585:Nitrogen Dioxide / Q000378:metabolism; D009589:Nitrogen Oxides / Q000378:metabolism; D011817:Rabbits; D012486:Salmonella typhimurium; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology*; D014605:Uveitis / Q000139:chemically induced / Q000378:metabolism*
D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D009589:Nitrogen Oxides; C118852:S,S'-1,4-phenylene-bis(1,2-ethanediyl)bis-isothiourea; C031701:nitrogen trioxide; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D013890:Thiourea; D009585:Nitrogen Dioxide; D019331:NG-Nitroarginine Methyl Ester