Mechanisms of magnesium-induced vasodilation in cerebral penetrating arterioles.
Mechanisms of magnesium-induced vasodilation in cerebral penetrating arterioles.
复制标题
DOI：
10.1016/j.neures.2015.12.005
复制
发表时间：
2016-06
影响因子：
2.9
通讯作者：
Dacey RG Jr
中科院分区：
文献类型：
--
作者：
Murata T;Dietrich HH;Horiuchi T;Hongo K;Dacey RG Jr
我们在脑穿通小动脉中研究了细胞外镁诱导的血管舒张的信号传导机制和剂量依赖性，以及其在SAH后与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。对雄性大鼠穿透性小动脉进行插管。监测其内径。为了研究镁诱导的血管舒张的机制，测试了内皮功能、钾通道和内皮损伤的抑制剂。为了模拟脑血管痉挛，我们应用了几种致痉挛激动剂。增加细胞外镁浓度产生浓度依赖性血管舒张，这是部分衰减的非特异性钙敏感性钾通道抑制剂四乙铵，但不是由其他钾通道抑制剂。一氧化氮合酶抑制剂L-NNA和空气栓塞引起的内皮损伤都不能减少扩张。虽然镁引起的血管舒张作用可被致痉剂ET-1轻微减弱，但PF 2 α和TXA 2类似物的应用均不影响血管舒张作用。镁诱导脑穿通小动脉的浓度依赖性和平滑肌细胞依赖性扩张。平滑肌细胞钙敏感性钾通道在镁诱导的血管舒张中起关键作用。镁也扩张内皮受损的血管以及血管预收缩与痉挛激动剂。这些结果为镁的临床应用提供了基本背景，特别是在治疗SAH后迟发性脑缺血或血管痉挛方面。
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.