The role of nitric oxide in experimental allergic conjunctivitis.
OBJECTIVE
To evaluate the role of nitric oxide (NO) in the pathogenesis of allergic conjunctivitis and the effect of NO-synthase (NOS) inhibitors.


METHODS
The experimental allergic conjunctivitis was provoked in rabbits and healthy human volunteers by mast cell activators (codeine phosphate, 2.5 mg/mL; compound 48/80, 50 mg/mL; and lipopolysaccharide, 10 ng/eye). NOS inhibitors (aminoguanidine [AG], 1.5%, or N(G)-nitro-L-arginine methyl ester [L-NAME], 200 microg/eye) were applied as a pretreatment. In a rabbit model, concentrations of nitrite plus nitrate in the tear were measured colorimetrically using the Griess reaction after 0.5, 1.5, 3, 6, and 9 h. Immunohistochemical study for NOS was performed. The clinical scoring was performed in human volunteers. The vascular permeability was determined by measuring the albumin content in the tear of the challenged human eyes after 1 h.


RESULTS
After the instillation of mast cell activator, the NO level and clinical symptoms were markedly increased within 1.5 h. The NOS inhibitors suppressed the NO level. Vascular permeability was also increased in the activator-treated group. The NO-synthase immunoreactivity has been detected in the conjunctival subepithelial area and stroma for brain and endothelial isoform. L-NAME significantly reduces the immunoreactivity for NOS.


CONCLUSIONS
These results suggest that the expression of NOS mainly contributes to the allergic symptoms. Therefore, NO is an important factor in the induction and progress of the allergic reaction to ocular surface. The NOS inhibitors may have a beneficial effect for allergic conjunctivitis.
Ko
S M
SM
Department of Ophthalmology, Chung-ang University, College of Medicine, Yongsan-Gu, Seoul, Korea.
Kim
M K
MK
Kim
J C
JC
D000328:Adult; D000418:Albumins / Q000378:metabolism; D000818:Animals; D002199:Capillary Permeability; D003061:Codeine / Q000633:toxicity; D003233:Conjunctivitis, Allergic / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity; D008407:Mast Cells / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D009573:Nitrites / Q000378:metabolism; D011817:Rabbits; D013666:Tears / Q000378:metabolism
D000418:Albumins; D004791:Enzyme Inhibitors; D006146:Guanidines; D008070:Lipopolysaccharides; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; C496319:NOS2 protein, human; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C004479:pimagedine; D003061:Codeine; D019331:NG-Nitroarginine Methyl Ester