N-acetylcysteine-induced vasodilation involves voltage-gated potassium channels in rat aorta
N-acetylcysteine-induced vasodilation involves voltage-gated potassium channels in rat aorta
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N-乙酰半胱氨酸诱导的血管舒张涉及大鼠主动脉中的电压门控钾通道
DOI：
10.1016/j.lfs.2009.02.023
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发表时间：
2009-05-22
期刊：
影响因子：
6.1
通讯作者：
Gao, Ping Jin
中科院分区：
文献类型：
--
作者：
Han, Wei-Qing;Zhu, Ding-Liang;Gao, Ping Jin
目的：N-乙酰半胱氨酸 (NAC) 通过降低实验性高血压和人类高血压中的活性氧 (ROS) 水平，对血管功能障碍具有保护作用。本研究旨在探讨NAC在体外是否通过一氧化氮-环磷酸鸟苷(NO-cGMP)途径、细胞外Ca2+和/或K+通道舒张血管环。主要方法：将大鼠主动脉固定在器官浴中，用0.1、0.5或1μmol/L去氧肾上腺素收缩至平台期，在ROS存在或不存在的情况下考察NAC的血管舒张作用。 NO-cGMP 途径或 K+ 通道的清除剂、抑制剂。血管平滑肌细胞 (VSMC) 负载钙敏感荧光染料 Fluo-3 AM，并通过激光扫描共聚焦显微镜测定 [Ca2+](i)。 主要发现：用去氧肾上腺素预收缩 NAC (0.1-4 mmol/L)，剂量依赖性地松弛大鼠主动脉。内皮去除、内皮一氧化氮合酶抑制剂N-omega-Nitro-L-精氨酸(L-NNA)(100μmol/L)或可溶性鸟苷酸环化酶(sGC)抑制剂(ODQ)(10μmol/L)不影响NAC诱导的血管舒张。相比之下，去除细胞外钙后，NAC 诱导的血管舒张作用减弱，钙成像显示 4 mmol/L NAC 快速降低加载 Fluo-3 AM 的 VSMC 中的 [Ca2+](i)。在电压门控 K+ 通道 (Kv) 抑制剂 4-氨基吡啶 (4-AP) 存在下，NAC 诱导的血管舒张作用显着降低。意义：NAC 的血管舒张作用至少部分可以通过电压门控 K+ 通道的激活来解释。 (C) 2009 Elsevier Inc. 保留所有权利。
Aims: N-acetylcysteine (NAC) has a protective effect against vascular dysfunction by decreasing the level of reactive oxygen species (ROS) in experimental and human hypertension. This study was designed to examine whether NAC would relax vascular rings in vitro via nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway, extracellular Ca2+ and/or K+ channels.Main methods: Rat aortic arteries were mounted in an organ bath, contracted with 0.1, 0.5 or 1 mu mol/L phenylephrine to plateau, and the vasodilatory effect of NAC was examined in the absence or presence of ROS scavengers, inhibitors of NO-cGMP pathway or K+ channels. Vascular smooth muscle cells (VSMCs) were loaded with a calcium sensitive fluorescent dye fluo-3 AM, and [Ca2+](i) was determined with laser-scanning confocal microscopy.Key findings: NAC (0.1-4 mmol/L) dose-dependently relaxed rat aorta pre-contracted with phenylephrine. Endothelium removal, endothelial nitric oxide synthase inhibitor N-omega-Nitro-L-arginine (L-NNA) (100 mu mol/L) or soluble guanylyl cyclase (sGC) inhibitor (ODQ) (10 mu mol/L) did not affect NAC-induced vasodilation. In contrast, NAC-induced vasodilation was blunted after extracellular calcium was removed and calcium imaging showed that 4 mmol/L NAC quickly decreased [Ca2+](i) in fluo-3 AM loaded VSMCs. NAC-induced vasodilation was significantly reduced in the presence of voltage-gated K+ channels (Kv) inhibitor 4-aminopyridine (4-AP).Significance: The vasodilatory effect of NAC may be explained at least partly by activation of voltage-gated K+ channels. (C) 2009 Elsevier Inc. All rights reserved.