Nitric oxide mediates mucin secretion in endotoxin-induced otitis media with effusion

The mechanisms that regulate mucin release in chronic otitis media with effusion, a lead-ing cause of hearing loss in children, remain largely unknown. We developed an animal model using Sprague-Dawley rats to determine the factors responsible for mucin produc-tion in chronic otitis media with effusion. N-nitro-L-arginine methyl ester (L-NAME), a com-petitive inhibitor of nitric oxide synthase, was used to investigate the role of nitric oxide in mucin secretion by the middle ear epithelium. All rats underwent eustachian tube obstruc-tion. In the first set of rats, the middle ear was then injected transtympanically with 35 gl of either 300 mOsm Krebs-Ringer bicarbonate buffer (control group) or I mg/ml lipopolysac-charide in Krebs:Ringer (experimental group I). In a second set of rats, the middle ear space was injected with lipopolysaccharide and then infused at a continuous rate for 7 days with either Krebs-Ringer (experimental group 2) or I mmol/L L-NAME in Krebs-Ringer (experimental group 3) through an osmotic infusion pump. After 7 days the volume of effu-sion and the quantity of mucin collected were significantly greater in lipopolysaccharide-exposed ears than in controls. In addition, antimucin immunostaining demonstrated mucous cell hyperplasia in response to lipopolysaccharide. The lipopolysaccharide