NITRIC-OXIDE PLAYS A ROLE AS A MEDIATOR OF CONJUNCTIVAL EDEMA IN EXPERIMENTAL ALLERGIC CONJUNCTIVITIS

The role of nitric oxide in allergic conjunctivitis was studied in a g uinea pig model, The eyes of sensitized guinea pigs were challenged wi th ovalbumin (20 mu g per eye) or histamine (20 mu g per eye), Synthes is of nitric oxide (NO) was inhibited using L-NAME (200 mu g per eye) or aminoguanidine (200 mu g per eye). The formation of conjunctival ed ema was graded and levels of nitrite, a breakdown product of nitric ox ide were measured in lavage fluid., Conjunctival vasopermeability was determined by measuring the albumin concentration in the fluid on the surface of the eye (lavage fluid), Animals were treated with sodium ni troprusside (SNP) or phenylephrine after which histamine induced conju nctival vasopermeability changes were measured. Drugs were administere d topically with the other eye serving as a control. Both ovalbumin an d histamine produced a marked inflammatory response including hyperaem ia and edema. At the top of the inflammatory response occurring 30 min after challenge, increased levels of nitrite, a breakdown product of NO, were measured in lavage fluid. Prophylactic treatment with L-NAIME or aminoguanidine resulted in a significant inhibition of the NO synt hesis. Both L-NAME and aminoguanidine decreased conjunctival vascular permeability and edema formation significantly. Administration of SNP resulted in a marked dilatation of conjunctival blood vessels and prod uced a dose-dependent increase of vascular permeability. Addition of S NP to histamine significantly enhanced conjunctival edema and potentia ted vascular permeability. These results indicate that NO is produced in the acute phase of allergic conjunctivitis and mediates vasodilatat ion after topical provocation with ovalbumin or histamine in sensitize d guinea pigs. The resulting increase of the conjunctival blood flow s ubsequently increases the vascular permeability and enhances conjuncti val edema formation. Inhibition of NO synthesis leads to a reduction o f conjunctival hyperaemia and subsequently reduces the formation of ed ema. (C) 1996 Academic Press Limited