Interaction of nitric oxide, 20-HETE, and EETs during functional hyperemia in whisker barrel cortex
Interaction of nitric oxide, 20-HETE, and EETs during functional hyperemia in whisker barrel cortex
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DOI：
10.1152/ajpheart.01211.2007
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发表时间：
2008-08-01
影响因子：
4.8
通讯作者：
Koehler, Raymond C.
中科院分区：
文献类型：
--
作者：
Liu, Xiaoguang;Li, Chunyuan;Koehler, Raymond C.
一氧化氮（NO）在感觉激活过程中调节大脑皮层的血管舒张。已知NO抑制20-HETE的合成，20-HETE与脑切片中星形胶质细胞活化期间的小动脉收缩有关。我们测试的假设，衰减的脑血流量（CBF）的反应，须刺激后看到NO合酶（NOS）抑制需要20-HETE的合成和环氧二十碳三烯酸（ESTRA）拮抗剂的能力，以减少CBF的反应是钝化后NOS抑制，但恢复与同时封锁20-HETE合成。在麻醉大鼠中，7-硝基吲唑阻断神经元NOS后，刺激胡须时CBF的增加减弱。随后给予20-HETE合成抑制剂N-羟基-N '-（4-正丁基-2-甲基苯基）甲脒（HET 0016）使CBF反应恢复至对照水平。在给予7-硝基吲唑后，E2受体拮抗剂14，15-环氧二十碳-5（Z）-烯酸（14，15-EEZE）对CBF反应的抑制作用丧失，而同时给予7-硝基吲唑和HET 0016则恢复了14，15-EEZE的抑制作用。单独给予HET 0016对大鼠诱发的CBF反应只有很小的影响。此外，在神经元型NOS+/+和NOS-/-小鼠中，HET 0016给药不会增加CBF对触须刺激的反应。在神经元型NOS+/+小鼠中，HET 0016还阻断了急性NOS抑制中观察到的反应降低。这些结果表明，20-HETE的合成通常基本上不限制功能性充血。在功能激活过程中增加的NO产生可以动态地抑制20-HETE合成或下游信号传导，并允许EET依赖性血管舒张。随着小鼠神经元NOS的慢性丧失，其他机制明显抑制20-HETE合成或信号传导。
Nitric oxide (NO) modulates vasodilation in cerebral cortex during sensory activation. NO is known to inhibit the synthesis of 20-HETE, which has been implicated in arteriolar constriction during astrocyte activation in brain slices. We tested the hypothesis that the attenuated cerebral blood flow (CBF) response to whisker stimulation seen after NO synthase (NOS) inhibition requires 20-HETE synthesis and that the ability of an epoxyeicosatrienoic acids (EETs) antagonist to reduce the CBF response is blunted after NOS inhibition but restored with simultaneous blockade of 20-HETE synthesis. In anesthetized rats, the increase in CBF during whisker stimulation was attenuated after the blockade of neuronal NOS with 7-nitroindazole. Subsequent administration of the 20-HETE synthesis inhibitor N-hydroxy-N'-(4-n-butyl-2-methylphenyl) formamidine (HET0016) restored the CBF response to control levels. After the administration of 7-nitroindazole, the inhibitory effect of an EETs antagonist 14,15-epoxyeicosa-5(Z)-enoic acid (14,15-EEZE) on the CBF response was lost, whereas the simultaneous administration of 7-nitroindazole and HET0016 restored the inhibitory effect of 14,15-EEZE. The administration of HET0016 alone had only a small effect on the evoked CBF response in rats. Furthermore, in neuronal NOS+/+ and NOS-/- mice, HET0016 administration did not increase the CBF response to whisker stimulation. In neuronal NOS+/+ mice, HET0016 also blocked the reduction in the response seen with acute NOS inhibition. These results indicate that 20-HETE synthesis normally does not substantially restrict functional hyperemia. Increased NO production during functional activation may act dynamically to suppress 20-HETE synthesis or downstream signaling and permit EETs-dependent vasodilation. With the chronic loss of neuronal NOS in mice, other mechanisms apparently suppress 20-HETE synthesis or signaling.