NITRIC-OXIDE MEDIATES MUCIN SECRETION IN ENDOTOXIN-INDUCED OTITIS-MEDIA WITH EFFUSION

The mechanisms that regulate mucin release in chronic otitis media wit h effusion, a leading cause of hearing loss in children, remain largel y unknown. We developed an animal model using Sprague-Dawley rats to d etermine the factors responsible for mucin production in chronic otiti s media with effusion. N-nitro-L-arginine methyl ester (L-NAME), a com petitive inhibitor of nitric oxide synthase, was used to investigate t he role of nitric oxide in mucin secretion by the middle ear epitheliu m. All rats underwent eustachian tube obstruction. In the first set of rats, the middle eat was then injected transtympanically with 35 mu l of either 300 mOsm Krebs-Ringer bicarbonate buffer (control group) or 1 mg/ml lipopolysaccharide in Krebs-Ringer (experimental group 1). In a second set of rats, the middle ear space was injected with lipopoly saccharide and then infused at a continuous rate for 7 days with eithe r Krebs-Ringer (experimental group 2) or 1 mmol/L L-NAME in Krebs-Ring er (experimental group 3) through an osmotic infusion pump. After 7 da ys the volume of effusion and the quantity of mucin collected were sig nificantly greater in lipopolysaccharide-exposed ears than in controls . In addition, antimucin immunostaining demonstrated mucous cell hyper plasia in response to lipopolysaccharide. The lipopolysaccharide-induc ed production of mucin and mucous cell hyperplasia was inhibited in ea rs treated with lipopolysaccharide and L-NAME. These results suggest t hat nitric oxide is a mediator in the pathway of mucin secretion in ch ronic otitis media with effusion.