Faculty Collaboration Database

Endotoxin-induced uveitis in the rat is attenuated by inhibition of nitric oxide production. Invest Ophthalmol Vis Sci 1994 Jul;35(8):3278-88

Date

07/01/1994

Pubmed ID

7519183

Scopus ID

2-s2.0-0028141504 (requires institutional sign-in at Scopus site)   111 Citations

Abstract

PURPOSE: 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.

Author List

Tilton RG, Chang K, Corbett JA, Misko TP, Currie MG, Bora NS, Kaplan HJ, Williamson JR

Author

John A. Corbett PhD Chair, Professor in the Biochemistry department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Albumins
Amino Acid Oxidoreductases
Animals
Aqueous Humor
Bacterial Toxins
Capillary Permeability
Endotoxins
Guanidines
Hemodynamics
Leukocyte Count
Male
Nitrates
Nitric Oxide
Nitric Oxide Synthase
Rats
Rats, Inbred Lew
Regional Blood Flow
Salmonella
Uveitis