Akgören N, Fabricius M, Lauritzen M
Laboratory of Clinical Neurophysiology, Rigshospitalet, Copenhagen, Denmark.
Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):5903-7. doi: 10.1073/pnas.91.13.5903.
The endothelium-derived relaxing factor, probably nitric oxide (NO), is a potent vasodilator that regulates the vascular tone in several vascular beds, including the brain. We explored the possibility that NO might be of importance for the increase of cerebral blood flow (CBF) associated with activity of the well-defined neuronal circuits of the rat cerebellar cortex. Laser-Doppler flowmetry was used to measure increases of cerebellar blood flow evoked by trains of electrical stimulations of the dorsal surface. The evoked increases of CBF were frequency-dependent, being larger on than off the parallel fiber tracts, suggesting that conduction along parallel fibers and synaptic activation of target cells were important for the increase of CBF. This was verified experimentally since the evoked CBF increases were abolished by tetrodotoxin and reduced by 10 mM Mg2+ and selective antagonists for non-N-methyl-D-aspartate receptors. The cerebellar cortex contains high levels of NO synthase. This raised the possibility that NO was involved in the increase of CBF associated with neuronal activation. NO synthase inhibition by topical application of NG-nitro-L-arginine attenuated the evoked CBF increase by about 50%. This effect was partially reversed by pretreatment with L-arginine, the natural substrate for the enzyme, while NG-nitro-D-arginine, the inactive enantiomer, had no effect on the evoked CBF increases. Simultaneous blockade of non-N-methyl-D-aspartate receptors and NO synthase had no further suppressing effect on the blood flow increase than either substance alone, suggesting that the NO-dependent flow rise was dependent on postsynaptic mechanisms. These findings are consistent with the idea that local synthesis of NO is involved in the transduction mechanism between neuronal activity and increased CBF.
内皮源性舒张因子，可能是一氧化氮（NO），是一种强效血管舒张剂，可调节包括脑在内的多个血管床的血管张力。我们探讨了NO对于与大鼠小脑皮质明确的神经回路活动相关的脑血流量（CBF）增加可能具有重要作用的可能性。使用激光多普勒血流仪测量背表面电刺激串诱发的小脑血流量增加。诱发的CBF增加呈频率依赖性，在平行纤维束上比在其外更大，这表明沿平行纤维的传导和靶细胞的突触激活对于CBF增加很重要。这通过实验得到了验证，因为诱发的CBF增加被河豚毒素消除，并被10 mM Mg2+和非N-甲基-D-天冬氨酸受体的选择性拮抗剂降低。小脑皮质含有高水平的一氧化氮合酶。这增加了NO参与与神经元激活相关的CBF增加的可能性。局部应用NG-硝基-L-精氨酸抑制一氧化氮合酶使诱发的CBF增加减弱约50%。用该酶的天然底物L-精氨酸预处理可部分逆转此效应，而无活性对映体NG-硝基-D-精氨酸对诱发的CBF增加无影响。同时阻断非N-甲基-D-天冬氨酸受体和一氧化氮合酶对血流增加的抑制作用并不比单独使用任何一种物质更强，这表明依赖NO的血流增加依赖于突触后机制。这些发现与局部合成的NO参与神经元活动与CBF增加之间的转导机制这一观点一致。
