Light-induced vs. bradykinin-induced relaxation of coronary arteries: do S-nitrosothiols act as endothelium-derived hyperpolarizing factors?
Light-induced vs. bradykinin-induced relaxation of coronary arteries: do S-nitrosothiols act as endothelium-derived hyperpolarizing factors?
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DOI：
10.1097/hjh.0b013e32832bff54
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发表时间：
2009-08-01
影响因子：
4.9
通讯作者：
Danser, A. H. Jan
中科院分区：
文献类型：
--
作者：
Batenburg, Wendy W.;Kappers, Mariette H. W.;Danser, A. H. Jan
背景 光诱导的松弛依赖于 S-亚硝基硫醇。 S-亚硝基硫醇还可以作为内皮源性超极化因子，介导猪冠状动脉 (PCA) 对缓激肽的松弛反应。在这里，我们比较了光诱导和缓激肽诱导的 PCA 松弛机制。方法 PCA 在黑暗中安装在器官浴中，预收缩并暴露于多色光（5 分钟）或 100 nmol/l 缓激肽。结果 光松弛 PCA 最大 71 +/- 1%。 S-亚硝基硫醇耗尽消除了这种松弛。重复光照后放松会减弱，特别是如果两次光照之间的黑暗期小于 10 分钟，并且在去除内皮或用 N-omega-硝基-L-精氨酸甲酯 (L-NAME) 阻断一氧化氮合酶后放松会增加，尽管后两个程序可以防止鸟苷-3',5'-环单磷酸的生成。因此，存储池的重新加载发生在黑暗中，内皮一氧化氮抑制该过程，并且光松弛不依赖于鸟苷-3',5'-环单磷酸。缓激肽使 PCA 放松 69 +/- 3%。一氧化氮清除剂羟钴胺和Na+-K+ ATP酶抑制剂哇巴因消除了对缓激肽和光的反应。鸟苷酸环化酶抑制剂 1H-[1,2,4] 恶二唑并[4,3-a] 喹喔啉-1-one 消除了对光的反应，并且与 L-NAME 一样，阻断了对缓激肽的反应超过 50%。除了 L-NAME 之外，中小电导 Ca2+ 依赖性 K+ 通道 (IKCa/SKCa) 阻断进一步降低了对缓激肽的反应并增强了光松弛。 结论 光松弛依赖于储存的 S-亚硝基硫醇，其释放/合成受到内皮一氧化氮和 IKCa/SKCa 的负面影响。 S-亚硝基硫醇激活内皮 IKCa/SKCa，并通过鸟苷酸环化酶激活平滑肌 Na+-K+ ATP 酶。因此，它们具有缓激肽诱导的内皮源性超极化因子的所有特性。 J Hypertens 27：1631-1640 (C) 2009 Wolters Kluwer Health |利平科特·威廉姆斯和威尔金斯。
Background Light-induced relaxation depends on S-nitrosothiols. S-Nitrosothiols may also serve as endothelium-derived hyperpolarizing factors, mediating the relaxant response of porcine coronary arteries (PCAs) to bradykinin. Here we compared the mechanism of light-induced and bradykinin-induced PCA relaxation.Methods PCAs were mounted in organ baths in the dark, preconstricted and exposed to polychromatic light (5 min) or 100 nmol/l bradykinin.Results Light relaxed PCAs by maximally 71 +/- 1%. S-Nitrosothiol depletion abolished this relaxation. Relaxations diminished following repetitive light exposures, particularly if the dark periods between the light exposures were less than 10 min, and increased following endothelium removal or nitric oxide synthase blockade with N-omega-nitro-L-arginine methyl ester (L-NAME), despite the prevention of guanosine-3',5'-cyclic monophosphate generation by the latter two procedures. Thus, reloading of the storage pools occurs in the dark, endothelial nitric oxide inhibits this process and photorelaxation does not depend on guanosine-3',5'-cyclic monophosphate. Bradykinin relaxed PCAs by 69 +/- 3%. The nitric oxide scavenger hydroxocobalamin and the Na+-K+ ATPase inhibitor ouabain abolished the responses to bradykinin and light. The guanylyl cyclase inhibitor 1H-[1,2,4] oxadiazolo[4,3-a] quinoxalin-1-one abolished the response to light, and, like L-NAME, blocked the response to bradykinin by more than 50%. On top of L-NAME, intermediate and small conductance Ca2+-dependent K+ channel (IKCa/SKCa) blockade further reduced the response to bradykinin and enhanced photorelaxation.Conclusion Photorelaxation depends on stored S-nitrosothiols and their release/synthesis is negatively affected by endothelial nitric oxide and IKCa/SKCa. S-Nitrosothiols activate endothelial IKCa/SKCa and, via guanylyl cyclase, smooth muscle Na+-K+ ATPase. Thus, they possess all properties of a bradykinin-induced endothelium-derived hyperpolarizing factor. J Hypertens 27:1631-1640 (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins.