INHIBITION OF NITRIC-OXIDE SYNTHASE CAUSES ELEVATION OF HEARING THRESHOLDS

OBJECTIVE: Nitric oxide mediates the effects of excitatory amino acids in the central nervous system. The excitatory amino acids are thought to be the neurotransmitters at the cochlear hair cell-afferent nerve synapse. Nitric oxide synthase is present in spiral ganglion cells, Th is study investigated the role of nitric oxide in cochlear neurotransm ission. METHODS: In gerbils, cochlear compound action potential thresh olds were recorded before and after cochlear perfusions with control s olutions of artificial perilymph solution and test solutions of S-meth yl-L-thiocitrulline (MTC), a competitive inhibitor of nitric oxide syn thase. Cochleas were also preperfused with L-arginine before perfusion with a mixture of MTC/L-arginine (to overcome competitive inhibition by MTC with L-arginine, the natural substrate of nitric oxide synthase ), RESULTS: Cochlear perfusion with MTC caused significant elevations of compound action potential threshold of 51 dB as opposed to insignif icant elevations of only in dB in control animals. An insignificant th reshold shift of 9 dB was observed when L-arginine was coperfused with MTC, CONCLUSIONS: Nitric oxide is involved in neurotransmission/neuro modulation in the cochlea, Because nitric oxide is both a mediator of neurotoxicity and an initiator of apoptosis in the central nervous sys tem, nitric oxide may play a role in these processes in the cochlea.