ATP-INDUCED COCHLEAR BLOOD-FLOW CHANGES INVOLVE THE NITRIC-OXIDE PATHWAY

Although control mechanisms of cochlear blood flow (CBF) have been int ensively studied since laser Doppler flowmetry was introduced for CBF measurement in animals and humans, the role of adenosine 5'-triphospha te (ATP) in CBF regulation is not known. Since ATP is a potent vasoact ive agent in other organs, the aim of this study is to examine ATP-ind uced changes in CBF and to test whether the nitric oxide pathway is in volved in ATP-induced CBF changes. The anterior inferior cerebellar ar tery (AICA) of anesthetized pigmented guinea pigs was exposed, and ATP was perfused into the AICA. For CBF measurement, the bulla was opened and the 0.7 mm laser probe of a Perimed PF2B flowmeter was positioned on the basal turn of the cochlea. AICA perfusion of an ATP solution c aused dose-dependent transient CBF increases. The maximum CBF increase induced was 220% of the baseline. In some animals, CBF showed a dual effect; a transient decrease followed by a longer-lasting increase. Th e perfusions of sodium nitroprusside (SNP) also resulted in dose-depen dent CBF changes. The intravenous application of N-omega-nitro-L-argin ine methyl ester (L-NAME) significantly attenuated ATP-induced CBF inc reases, and enhanced ATP-induced decreases, but did not affect SNP-ind uced CBF changes. The ATP-induced CBF responses indicate that ATP play s a role in CBF regulation. The biphasic characteristic of the ATP-ind uced CBF change suggests the involvement of both Pt-2x- and P-2y-subty pe purinoceptors. That L-NAME caused attenuation of the ATP-induced CB F increase implies that the ATP-induced CBF increase is mediated by th e release of endothelium-derived relaxing factor, nitric oxide, follow ing activation of endothelial P-2y-purinoceptors in the cochlear vascu lar bed and/or cochlear supplying vessels.