Possible roles of nitric oxide in the physiology and pathophysiology of the mammalian cochlea.

Abstract

Nitric oxide (NO) has been implicated as a mediator of vasodilation and neurotransmission in the mammalian cochlea. This is demonstrated by the presence of nitric oxide synthase (NOS) and nitric oxide (NO) in the blood vessels and the organ of Corti in the cochlea. It is not certain if the neurons in the spiral ganglion produce NO since no fluorescent signal could be detected by 4,5-diaminofluorescein diacetate (DAF-2DA), a fluorescent indicator of NO. To determine if NO/peroxynitrite plays any role in neurodestruction observed in ischemic cochlea of the guinea pig, the effects of NO donors, such as S-nitrosocysteine (S-NC) and nitroglycerine (NTG); peroxynitrite generators, such as 3-morpholinosydnonimine (SIN-1); peroxynitrite inhibitors, such as superoxide dismutase plus catalase (SOD/Cat); and NOS inhibitors, such as N(G)-nitro-L-arginine methyl ether (L-NAME) were tested on normal and ischemic cochleae. The level of NO in the cochlea after 20 to 120 minutes of ischemia was indicated by measurement of nitrites/nitrates in the perilymph. The evidence gathered from these experiments indicates that NO or peroxynitrite is not necessarily destructive to auditory hair cells, and in fact, exogenous NO may protect neural structures in the cochlea from damage under ischemic conditions.