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

被引:16
作者
Kamata, K
Inazu, M
Takeda, H
Goto, H
Matsumiya, T
Usui, M
机构
[1] Tokyo Med Univ, Dept Pharmacol, Shinjuku Ku, Tokyo 1608402, Japan
[2] Tokyo Med Univ, Intractable Dis Res Ctr, Shinjuku Ku, Tokyo 1608402, Japan
[3] Tokyo Med Univ, Dept Ophthalmol, Shinjuku Ku, Tokyo 1600023, Japan
关键词
nitric oxide; endotoxin-induced uveitis; inducible nitric oxide synthase; microdialysis;
D O I
10.1016/S1043-6618(03)00057-4
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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.
引用
收藏
页码:485 / 491
页数:7
相关论文
共 34 条
[1]   ANTAGONISTIC ACTION OF IMIDAZOLINEOXYL N-OXIDES AGAINST ENDOTHELIUM-DERIVED RELAXING FACTOR .NO THROUGH A RADICAL REACTION [J].
AKAIKE, T ;
YOSHIDA, M ;
MIYAMOTO, Y ;
SATO, K ;
KOHNO, M ;
SASAMOTO, K ;
MIYAZAKI, K ;
UEDA, S ;
MAEDA, H .
BIOCHEMISTRY, 1993, 32 (03) :827-832
[2]   Nitric oxide synthase inhibitors exert differential time-dependent effects on LPS-induced uveitis [J].
Allen, JB ;
McGahan, MC ;
Ferrell, JB ;
Adler, KB ;
Fleisher, LN .
EXPERIMENTAL EYE RESEARCH, 1996, 62 (01) :21-28
[3]   GLIBENCLAMIDE AND L-N(G)-NITRO-ARGININE METHYL-ESTER MODULATE THE OCULAR AND HYPOTENSIVE EFFECTS OF CALCITONIN GENE-RELATED PEPTIDE [J].
ANDERSSON, SE .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1992, 224 (01) :89-91
[4]   Quantitative determination of endogenous nitric oxide in the mouse skin in vivo by microdialysis [J].
Andoh, T ;
Kuraishi, Y .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1997, 332 (03) :279-282
[5]   Nitric oxide in the eye: Multifaceted roles and diverse outcomes [J].
Becquet, F ;
Courtois, Y ;
Goureau, O .
SURVEY OF OPHTHALMOLOGY, 1997, 42 (01) :71-82
[6]   Nitric oxide and the immune response [J].
Bogdan, C .
NATURE IMMUNOLOGY, 2001, 2 (10) :907-916
[7]   NITRIC-OXIDE - A PHYSIOLOGICAL MESSENGER MOLECULE [J].
BREDT, DS ;
SNYDER, SH .
ANNUAL REVIEW OF BIOCHEMISTRY, 1994, 63 :175-195
[8]  
FORSTERMANN U, 1995, N-S ARCH PHARMACOL, V352, P351
[9]  
GARVEY EP, 1994, J BIOL CHEM, V269, P26669
[10]   NITRIC-OXIDE SYNTHASE INHIBITORS PROTECT RAT RETINA AGAINST ISCHEMIC-INJURY [J].
GEYER, O ;
ALMOG, J ;
LUPUMEIRI, M ;
LAZAR, M ;
ORON, Y .
FEBS LETTERS, 1995, 374 (03) :399-402