Inhibition of inducible nitric oxide synthase lowers the cochlear damage by lipopolysaccharide in guinea pigs

Endotoxin-treated cochleas of the guinea pig were examined electrophysiolog ically and immunohistochemically concerning the expression of inducible nit ric oxide synthase (iNOS/NOS II). One mg of bacterial lipopolysaccharide (L PS, 5 mg/ml) or mixed solution of 1 mg of LPS plus 1 mg of N-G-nitro-L-argi nine methyl eater (L-NAME, 5 mg/ml) (L-NAME/LPS) was injected into the midd le ear of guinea pigs transtympanically. The electrocochleograms were measu red prior to, immediately and 48 h after the injection. Immunohistological studies for iNOS followed after fixation, embedding and sectioning of the t emporal bones. The threshold and amplitude of the compound action potential (CAP) became s ignificantly worse in the LPS treated group. In contrast, the changes of th e threshold and amplitude of CAP were decreased in the L-NAME/LPS group, iN OS was expressed in the stria vascularis, the spiral ligament, the organ of Corti and the spiral ganglion in the LPS group. These immunoreactivities i n the L-NAME/LPS group were less intense than that in the LPS group. These results indicate that LPS has an ototoxic effect on the cochlea and that th is effect could be mediated by iNOS produced high nitric oxide under inflam matory conditions.