Murata Takahiro, Dietrich Hans H, Horiuchi Tetsuyoshi, Hongo Kazuhiro, Dacey Ralph G
Department of Neurosurgery, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO 63110, United States; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, United States.
Neurosci Res. 2016 Jun;107:57-62. doi: 10.1016/j.neures.2015.12.005. Epub 2015 Dec 19.
We investigated in cerebral penetrating arterioles the signaling mechanisms and dose-dependency of extracellular magnesium-induced vasodilation and also its vasodilatory effects in vessels preconstricted with agonists associated with delayed cerebral vasospasm following SAH. Male rat penetrating arterioles were cannulated. Their internal diameters were monitored. To investigate mechanisms of magnesium-induced vasodilation, inhibitors of endothelial function, potassium channels and endothelial impairment were tested. To simulate cerebral vasospasm we applied several spasmogenic agonists. Increased extracellular magnesium concentration produced concentration-dependent vasodilation, which was partially attenuated by non-specific calcium-sensitive potassium channel inhibitor tetraethylammonium, but not by other potassium channel inhibitors. Neither the nitric oxide synthase inhibitor L-NNA nor endothelial impairment induced by air embolism reduced the dilation. Although the magnesium-induced vasodilation was slightly attenuated by the spasmogen ET-1, neither application of PF2α nor TXA2 analog effect the vasodilation. Magnesium induced a concentration- and smooth muscle cell-dependent dilation in cerebral penetrating arterioles. Calcium-sensitive potassium channels of smooth muscle cells may play a key role in magnesium-induced vasodilation. Magnesium also dilated endothelium-impaired vessels as well as vessels preconstricted with spasmogenic agonists. These results provide a fundamental background for the clinical use of magnesium, especially in treatment against delayed cerebral ischemia or vasospasm following SAH.
我们研究了脑穿透小动脉中细胞外镁离子诱导血管舒张的信号传导机制、剂量依赖性,以及其在与蛛网膜下腔出血(SAH)后迟发性脑血管痉挛相关的激动剂预收缩血管中的血管舒张作用。将雄性大鼠的穿透小动脉插管。监测其内径。为了研究镁离子诱导血管舒张的机制,测试了内皮功能抑制剂、钾通道抑制剂和内皮损伤情况。为了模拟脑血管痉挛,我们应用了几种致痉挛激动剂。细胞外镁离子浓度升高产生浓度依赖性血管舒张,非特异性钙敏感钾通道抑制剂四乙铵可部分减弱这种舒张,但其他钾通道抑制剂则无此作用。一氧化氮合酶抑制剂L-NNA和空气栓塞诱导的内皮损伤均未降低这种舒张。尽管镁离子诱导的血管舒张被致痉剂ET-1轻微减弱,但应用PF2α或TXA2类似物均不影响血管舒张。镁离子在脑穿透小动脉中诱导浓度和平滑肌细胞依赖性舒张。平滑肌细胞的钙敏感钾通道可能在镁离子诱导的血管舒张中起关键作用。镁离子还可使内皮损伤的血管以及用致痉挛激动剂预收缩的血管舒张。这些结果为镁离子的临床应用提供了基本背景,尤其是在治疗SAH后的迟发性脑缺血或血管痉挛方面。