The role of nitric oxide synthase in endotoxin-induced uveitis: effects of NG-nitro L-arginine.
OBJECTIVE
To evaluate the role of nitric oxide synthase (NOS) in endotoxin-induced uveitis (EIU).


METHODS
EIU was caused in Lewis rats by injecting lipopolysaccharide (LPS) into the foot pad, and the effects of an NOS inhibitor, NG-nitro L-arginine (NA), was comparatively studied by the simultaneous administration of NA and LPS. Total NOS and inducible NOS (iNOS) activities were differentially assayed in the anterior segment of the eye in EIU with and without NA treatment. The effects of NA on EIU were also evaluated by clinical manifestation, histology, and protein concentration in the aqueous humor.


RESULTS
In untreated rats, there was no significant iNOS activity. With the EIU model, iNOS activity showed a marked increase in the anterior segment of the eye, reaching a maximum 9 hours after LPS injection (10,850 +/- 1,650 cpm/mg protein, mean +/- SEM). NA reduced the iNOS activity 9 hours after injection to 2,400 +/- 90 cpm/mg protein (P < 0.001). Aqueous humor protein concentration in the EIU model was 10.6 +/- 0.75 mg/ml, and the cell number was 216 +/- 12 cells/microliters. NA significantly reduced these factors to 4.25 +/- 0.48 mg/microliters for the protein concentration (P < 0.0005) and 25 +/- 6 cells/ml for the cell number (P < 0.0005). Histologic studies showed less prominent infiltration of polymorphonuclear cells in the anterior uvea than for conventional EIU.


CONCLUSIONS
Induction of iNOS may play a key role in the pathogenesis of EIU. Because inhibition of iNOS activity reduced the inflammatory response, suppression of NO formation may inhibit the development of EIU.
Mandai
M
M
Department of Ophthalmology, Kyoto University, Faculty of Medicine, Japan.
Yoshimura
N
N
Yoshida
M
M
Iwaki
M
M
Honda
Y
Y
D000594:Amino Acid Oxidoreductases / Q000502:physiology*; D000818:Animals; D000869:Anterior Eye Segment / Q000201:enzymology; D001082:Aqueous Humor / Q000378:metabolism; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001427:Bacterial Toxins; D004195:Disease Models, Animal; D004731:Endotoxins; D004768:Enterotoxins; D004790:Enzyme Induction / Q000187:drug effects; D005136:Eye Proteins / Q000378:metabolism; D007958:Leukocyte Count; D008297:Male; D009504:Neutrophils / Q000378:metabolism; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D051381:Rats; D011917:Rats, Inbred Lew; D012475:Salmonella; D014606:Uveitis, Anterior / Q000201:enzymology* / Q000209:etiology / Q000473:pathology
D001427:Bacterial Toxins; D004731:Endotoxins; D004768:Enterotoxins; D005136:Eye Proteins; C027952:salmonella toxin; D019335:Nitroarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases