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

Two nitric oxide synthase isoforms (NOS-I and NOS-III) are present in the mammalian cochlea, and many regulatory functions of the inner ear could be mediated by NO. In this study, cochlear potentials and immunohistochemical measures were analyzed by changing the concentration of NO in the guinea pig during intracochlear and intravenous application of an NOS inhibitor and an NO donor. In anesthetized guinea pigs the NOS inhibitor NG-nitro-L-arginine-methylester (L-NAME) was applied by intracochlear perfusion or intravenously. The cochlear potentials and blood pressure were measured during and after the application. Cochleae were removed and prepared for morphological and immunohistochemical examinations by light and electron microscopy. The same series of experiments was performed with the NO donor S-nitroso-N-acetyl-penicillamine (SNAP). Cochlear potentials were not altered during intracochlear perfusion or intravenous application of L-NAME or SNAP. With intravenous application of the substances, significant alterations in the systemic blood pressure were seen. No morphological alterations were noted but in the immunohistochemical investigations significant changes were detected by electron microscopy. Several possible functions of NO in the inner and outer hair cells, stria vascularis and ganglion cells are discussed. Our results suggest that NO has a major effect on the physiology of the inner and outer hair cells.