IMPORTANCE OF NITRIC-OXIDE FOR LOCAL INCREASES OF BLOOD-FLOW IN RAT CEREBELLAR CORTEX DURING ELECTRICAL-STIMULATION
IMPORTANCE OF NITRIC-OXIDE FOR LOCAL INCREASES OF BLOOD-FLOW IN RAT CEREBELLAR CORTEX DURING ELECTRICAL-STIMULATION
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DOI：
10.1073/pnas.91.13.5903
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发表时间：
1994-06-21
影响因子：
11.1
通讯作者：
LAURITZEN, M
中科院分区：
文献类型：
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作者：
AKGOREN, N;FABRICIUS, M;LAURITZEN, M
内皮源性舒张因子，可能是一氧化氮 (NO)，是一种有效的血管扩张剂，可调节包括大脑在内的多个血管床的血管张力。我们探讨了 NO 可能对于脑血流量 (CBF) 的增加具有重要意义的可能性，而脑血流量 (CBF) 与大鼠小脑皮质明确的神经元回路的活动相关。激光多普勒血流测定法用于测量背表面电刺激序列引起的小脑血流量的增加。 CBF 的诱发增加是频率依赖性的，平行纤维束上的增加大于平行纤维束外的增加，表明沿平行纤维的传导和靶细胞的突触激活对于 CBF 的增加很重要。这已通过实验得到验证，因为引起的 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。这提出了 NO 参与与神经元激活相关的 CBF 增加的可能性。局部应用 N-G-硝基-L-精氨酸抑制 NO 合酶，可将引起的 CBF 增加减弱约 50%。通过 L-精氨酸（该酶的天然底物）预处理可部分逆转这种效应，而 NG-硝基-D-精氨酸（非活性对映体）对引起的 CBF 增加没有影响。同时阻断非N-甲基-D-天冬氨酸受体和NO合酶对血液中的血液增加没有比单独使用任何一种物质更进一步的抑制作用，这表明NO依赖的血液增加依赖于突触后机制。这些发现与 NO 的局部合成参与神经元活动和 CBF 增加之间的转导机制的观点一致。
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 dow (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 N-G-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 now increase than either substance alone, suggesting that the NO-dependent now 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.