ATP-induced cochlear blood flow changes involve the nitric oxide pathway

Although control mechanisms of cochlear blood flow (CBF) have been intensively studied since laser Doppler flowmetry was introduced for CBF measurement in animals and humans, the role of adenosine 5'-triphosphate (ATP) in CBF regulation is not known. Since ATP is a potent vasoactive agent in other organs, the aim of this study is to examine ATP-induced changes in CBF and to test whether the nitric oxide pathway is involved in ATP-induced CBF changes. The anterior inferior cerebellar artery (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 caused 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. The perfusions of sodium nitroprusside (SNP) also resulted in dose- dependent CBF changes. The intravenous application of N(w)-nitro-L-arginine methyl ester (L-NAME) significantly attenuated ATP-induced CBF increases, and enhanced ATP-induced decreases, but did not affect SNP-induced CBF changes. The ATP-induced CBF responses indicate that ATP plays a role in CBF regulation. The biphasic characteristic of the ATP-induced CBF change suggests the involvement of both P(2x)- and P(2y)-subtype purinoceptors. That L-NAME caused attenuation of the ATP-induced CBF increase implies that the ATP-induced CBF increase is mediated by the release of endothelium-derived relaxing factor, nitric oxide, following activation of endothelial P(2y)- purinoceptors in the cochlear vascular bed and/or cochlear supplying vessels.