title: Electrophysiological and morphological evaluation of the acute ototoxicity of sodium nitroprusside.
abstract: Nitric oxide (NO) is a messenger molecule that mediates several physiological functions and pathological processes. Sodium nitroprusside (SNP), a potent vasodilator, when given clinically as an anti-hypertension agent, exerts its function by releasing NO. It was reported recently that SNP causes a loss of auditory nerve compound action potential (CAP) after topical application of SNP on guinea pig round window membrane (RWM). The current study was designed to investigate the ototoxic target of SNP through both electrophysiological and morphological approaches. The CAP threshold at frequencies ranging from 2 to 36 kHz, the cochlear microphonic quadratic distortion product (cmQDP, F2-F1, where F1 = 17.1 kHz; F2 = 18 kHz), and the cochlear microphonic (CM) at the frequency of F1 were recorded via a round window electrode before and up to 2 h after RWM application of 1 microliter of drug solution. Cochlear blood flow (CBF) and arterial blood pressure were monitored. The cochleae were then processed for morphological examination. The effect of SNP on endocochlear potential (EP) was also studied. Results showed that cmQDP, CM, and CAP, as well as EP, were suppressed in varying amounts, while CBF was substantially increased following drug application. Morphological evaluations showed swelling of the afferent inner radial dendrites within the basal cochlear turn in the higher concentration groups of SNP, while the hair cells presented no evidence of damage at the light microscopic level. The results indicate that SNP has an acute ototoxic effect in a concentration- and time-dependent manner. The targets of SNP ototoxicity are at least the afferent dendrites and stria vascularis.
authors.affiliation: Kresge Hearing Research Institute, University of Michigan, Ann Arbor 48109-0506, USA.
authors.forename: W J
authors.initials: WJ
authors.lastname: Kong
authors.forename: T
authors.initials: T
authors.lastname: Ren
authors.forename: A L
authors.initials: AL
authors.lastname: Nuttall
mesh_terms: D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D001489:Basilar Membrane / Q000187:drug effects / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003051:Cochlea / Q000098:blood supply / Q000187:drug effects*; D003055:Cochlear Microphonic Potentials / Q000187:drug effects*; D004594:Electrophysiology; D005260:Female; D006168:Guinea Pigs; D008297:Male; D008839:Microelectrodes; D009599:Nitroprusside / Q000633:toxicity*; D017084:Otoacoustic Emissions, Spontaneous; D012405:Round Window, Ear / Q000187:drug effects; D014432:Tympanic Membrane / Q000187:drug effects / Q000473:pathology; D014665:Vasodilator Agents / Q000633:toxicity*; D000159:Vestibulocochlear Nerve / Q000187:drug effects* / Q000378:metabolism
chemical_list: D014665:Vasodilator Agents; D009599:Nitroprusside