The mechanisms that regulate mucin release in chronic otitis media with effusion, a
leading 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 production
in chronic otitis media with effusion. N-nitro-l-arginine methyl
ester (l-NAME), a competitive 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 obstruction. In the first set of rats, the middle ear was
then injected transtympanically with 35 μl of either 300 mOsm Krebs-Ringer bicarbonate
buffer (control group) or 1 mg/ml lipopolysac-charide in Krebs-Ringer (experimental group
1). 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 1 mmol/L l-NAME in Krebs-Ringer (experimental group 3) through an osmotic
infusion pump. After 7 days the volume of effusion 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-induced production of mucin and mucous cell
hyperplasia was inhibited in ears treated with lipopolysaccharide and l-NAME.
These results suggest that nitric oxide is a mediator in the pathway of mucin secretion in
chronic otitis media with effusion.
