H2O2 is the transferrable factor mediating flow-induced dilation in human coronary arterioles.
H2O2 is the transferrable factor mediating flow-induced dilation in human coronary arterioles.
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DOI：
10.1161/circresaha.110.237636
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发表时间：
2011-03-04
影响因子：
20.1
通讯作者：
Gutterman DD
中科院分区：
文献类型：
--
作者：
Liu Y;Bubolz AH;Mendoza S;Zhang DX;Gutterman DD
内皮源性过氧化氢（H2O2）是调节人冠状小动脉（HCA）血流介导的扩张（FMD）通路的必要成分。然而，H2O2从来没有被证明是内皮依赖性的可转移超极化因子（EDHF）的剪切应力的反应。我们研究的假设，H2O2作为EDHF在HCA剪切应力。两个HCA串联插管（供体完整血管上游和内皮剥脱检测血管下游）。在无和有PEG-过氧化氢酶（PEG-CAT）的情况下检测了血流的直径变化。通过膜片钳技术检测了来自内皮完整的小动脉的灌流液下游的平滑肌细胞（SMC）中BKCa通道的开放状态概率。在一些实验中，使用与CAT结合的溴化氰活化的树脂柱从供体容器中除去H2O2。当血流从供体流向检测器时，两条血管均扩张（供体：68 ± 7%;检测器：45 ± 11%）。当血流方向相反时，只有供体血管扩张。仅接触检测血管的PEG-CAT阻断了该血管中的FMD（6 ± 4%），但未阻断供体血管中的FMD（61 ± 13%）。Paxilline抑制内皮剥脱的HCA对H2O2的扩张。供体血管流出物引起K+通道开放的伊比利亚毒素或PEG-CAT敏感的方式在细胞贴附补丁，但通道开放的影响不大，由内而外的补丁。当暴露于CAT柱流出物时，检测器血管的血管舒张减少。血流诱导内皮细胞产生H_2O_2，作为可转移的EDHF激活SMC上的BKCa通道。
Endothelial derived hydrogen peroxide (H2O2) is a necessary component of the pathway regulating flow-mediated dilation (FMD) in human coronary arterioles (HCA). However H2O2 has never been shown to be the endothelium-dependent transferrable hyperpolarization factor (EDHF) in response to shear stress. We examined the hypothesis that H2O2 serves as the EDHF in HCA to shear stress. Two HCAs were cannulated in series (a donor intact vessel upstream and endothelium-denuded detector vessel downstream). Diameter changes to flow were examined in the absence and presence of PEG-Catalase (PEG-CAT).The open state probability of BKCa channels in smooth muscle cells (SMC) downstream from the perfusate from an endothelium-intact arteriole was examined by patch clamping. In some experiments a cyanogen bromide activated resin column bound with CAT was used to remove H2O2 from the donor vessel. When flow proceeds from donor to detector, both vessels dilate (donor: 68±7%; detector: 45±11%). With flow in the opposite direction, only the donor vessel dilates. PEG-CAT contacting only the detector vessel blocked FMD in that vessel (6 ±4%) but not in donor vessel (61 ±13%). Paxilline inhibited dilation of endothelium-denuded HCA to H2O2. Effluent from donor vessels elicited K+ channel opening in an iberiotoxin - or PEG-CAT sensitive fashion in cell-attached patches, but had little effect on channel opening on inside-out patches. Vasodilation of detector vessels was diminished when exposed to effluent from CAT-column. Flow induced endothelial production of H2O2 which acts as the transferrable EDHF activating BKCa channels on the SMC.