Effects of nitric oxide on normal and ischemic cochlea of the guinea pig

To determine whether nitric oxide (NO)/peroxynitrite plays any role in neur odestruction observed in ischemic cochlea of the guinea pig, the effects of NO donors like S-nitrosocysteine (S-NC) and nitroglycerin (NTG), peroxynit rite generators like 3-morpholinosydnonimine (SIN-1), peroxynitrite inhibit ors like superoxide dismutase plus catalase (SOD/Cat), as well as NOS inhib itors like N-G-nitro-L-arginine methyl ether (L-NAME), were tested on norma l and ischemic cochleae. Various concentrations of S-NC and SIN-1 were intr oduced into the perilymphatic space of normal guinea pig cochlea, Quantitat ive scanning electron microscopy of inner and outer hair cells was carried out 2 days later. To determine the level of NO in the cochlea after 20 to 1 20 min of ischemia, nitrites/nitrates in the perilymph were measured. The e ffects of NO on the ischemic cochlea were tested by infusion of SOD/Cat, L- NAME, S-NC, and NTG; into the perilymphatic space just before decapitation. Introduction of fixative into the cochlea was delayed for 15 min to invest igate the effects of the chemicals on nerve endings at the base of inner ha ir cells. The results showed that the level of nitrites/nitrates tended to decline with increasing time of ischemia. There was no significant hair cel l loss in the cochleae treated with SIN-1 or S-NC. At 15 min after ischemia , most of the nerve endings at the base of the inner hair cells were protec ted from damage when 1 mM S-NC or NTG was infused into the perilymph, Taken together, the results indicate that NO/peroxynitrite is unlikely to be inv olved in the neurodestruction in the ischemic cochlea. In fact, exogenous N O may have a neural protective effect. (C) 2001 Academic Press.