The messenger molecule nitric oxide (NO) is involved in blood flow reg
ulation, cytotoxicity, and neural signalling, processes that are impor
tant in the physiology and pathophysiology of the mammalian cochlea. H
owever, neither the presence of NO nor its synthetic enzyme, NO syntha
se, has been established in the peripheral auditory system. NO synthas
e activity, measured as the enzymatic conversion of radioactive argini
ne to citrulline, was predominantly soluble in the auditory nerve, lat
eral wall, vestibule and cochlear neuroepithelium. N-methyl-L-arginine
and trifluoperazine inhibited NO synthase activity in the lateral wal
l and auditory nerve. Histochemical staining by NADPH-diaphorase local
ized NOS activity to the lateral wall and the neuronal elements of the
organ of Corti. Based on these results, the predominant NO synthase i
soform in the cochlea is the neuronal type-I isoform.