The vascular component of sodium salicylate ototoxicity in the guinea pig

Drugs of the salicylate family (aspirin-like drugs) are reversibly ototoxic. Electrophysiologic and ultrastructural evidence suggests an impairment of the sensory hair cells of the cochlea following salicylate treatment. In addition, since these drugs can cause vasoconstriction, the ototoxicity of salicylates may also involve an impairment of the blood circulation in inner ear. However, a vascular hypothesis of salicylate toxicity has not received much attention. In the current study, we simultaneously measured cochlear blood flow (by laser Doppler flowmetry) and the sound-evoked potentials from the round window. Sodium salicylate caused a decrease in cochlear blood flow that appeared within 30 min following an intramuscular injection of a low dose of sodium salicylate (100 mg/kg). This sodium salicylate dose did not cause a change in auditory sensitivity. For higher doses (200 mg/kg and 300 mg/kg), both cochlear blood flow and auditory sensitivity were affected. The 300 mg/kg dose decreased blood flow by about 25% and elevated compound action potential thresholds by 10 to 25 dB for high frequencies (≥ 8 kHz). Further experiments showed that salicylate-induced threshold shifts were significantly reduced for the mid-frequencies when cochlear blood flow is increased by the vasodilating drug hydralazine (negating the flow reduction caused by salicylate). These data indicate that in addition to the direct effect of systemically administered salicylate on neurosensory function a decreased blood flow contributes to the ototoxicity of salicylates.