Ren T, Nuttall A L, Miller J M
Oregon Hearing Research Center, Oregon Health Sciences University, Portland 97201-3098, USA.
Hear Res. 1997 Oct;112(1-2):87-94. doi: 10.1016/s0378-5955(97)00109-3.
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(omega)-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 P2x- and P2y-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 P2y-purinoceptors in the cochlear vascular bed and/or cochlear supplying vessels.
自从激光多普勒血流仪被用于测量动物和人类的耳蜗血流量（CBF）以来，人们对CBF的控制机制进行了深入研究，但三磷酸腺苷（ATP）在CBF调节中的作用尚不清楚。由于ATP在其他器官中是一种有效的血管活性物质，本研究的目的是研究ATP引起的CBF变化，并测试一氧化氮途径是否参与ATP引起的CBF变化。暴露麻醉的有色豚鼠的小脑前下动脉（AICA），并将ATP灌注到AICA中。为了测量CBF，打开鼓泡，将Perimed PF2B流量计的0.7毫米激光探头置于耳蜗的基底转上。向AICA灌注ATP溶液导致CBF呈剂量依赖性短暂增加。诱导的最大CBF增加为基线的220%。在一些动物中，CBF表现出双重作用；先是短暂下降，然后是持续时间更长的增加。硝普钠（SNP）灌注也导致CBF呈剂量依赖性变化。静脉注射N（ω）-硝基-L-精氨酸甲酯（L-NAME）显著减弱了ATP诱导的CBF增加，并增强了ATP诱导的下降，但不影响SNP诱导的CBF变化。ATP诱导的CBF反应表明ATP在CBF调节中起作用。ATP诱导的CBF变化的双相特征表明P2x和P2y亚型嘌呤受体均参与其中。L-NAME导致ATP诱导的CBF增加减弱，这意味着ATP诱导的CBF增加是由耳蜗血管床和/或耳蜗供血血管中的内皮P2y嘌呤受体激活后释放内皮源性舒张因子一氧化氮介导的。
