Endotoxin-induced uveitis in the rat is attenuated by inhibition of nitric oxide production.
OBJECTIVE
These experiments were undertaken to assess the role of increased nitric oxide production in the pathogenesis of vascular dysfunction associated with endotoxin-induced uveitis.


METHODS
Lipopolysaccharides (LPS) (100 micrograms of Salmonella minnesota) was injected into foot-pads of Lewis rats randomly assigned to an untreated group or to a group treated with subcutaneous injections of aminoguanidine, a selective inhibitor of the inducible isoform of nitric oxide synthase (iNOS). Controls included untreated and aminoguanidine-treated rats. Twenty to 24 hours later, blood flow and vascular 125I-albumin permeation were quantified in ocular tissues. Eyes were graded histologically for leukocyte infiltration into the anterior uvea and anterior chamber, and leukocyte counts were performed on aqueous fluid. Plasma nitrate levels were measured fluorometrically after enzymatic reduction to nitrite.


RESULTS
Lipopolysaccharides markedly increased plasma nitrate levels and 125I-albumin permeation in aqueous fluid, retina, anterior uvea, and choroid-sclera. Blood flow was increased only in the anterior uvea. Aminoguanidine normalized plasma nitrate levels and prevented or significantly ameliorated the 125I-albumin permeation and blood flow changes in ocular tissues. The increased aqueous fluid content of lymphocytes and neutrophils in LPS-treated rats, as well as the increased histologic score of iritis, were significantly reduced by aminoguanidine.


CONCLUSIONS
These results suggest that the hemodynamic and vascular permeability changes associated with endotoxin-induced uveitis are mediated in large part by increased production of nitric oxide.
Tilton
R G
RG
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri.
Chang
K
K
Corbett
J A
JA
Misko
T P
TP
Currie
M G
MG
Bora
N S
NS
Kaplan
H J
HJ
Williamson
J R
JR
D000418:Albumins / Q000493:pharmacokinetics; D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D001082:Aqueous Humor / Q000166:cytology / Q000378:metabolism; D001427:Bacterial Toxins; D002199:Capillary Permeability; D004731:Endotoxins; D006146:Guanidines / Q000494:pharmacology; D006439:Hemodynamics; D007958:Leukocyte Count; D008297:Male; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D019001:Nitric Oxide Synthase; D051381:Rats; D011917:Rats, Inbred Lew; D012039:Regional Blood Flow; D012475:Salmonella; D014605:Uveitis / Q000209:etiology / Q000378:metabolism*
D000418:Albumins; D001427:Bacterial Toxins; D004731:Endotoxins; D006146:Guanidines; D009566:Nitrates; C027952:salmonella toxin; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; C004479:pimagedine