Exercise training-enhanced, endothelium-dependent dilation mediated by altered regulation of BK(Ca) channels in collateral-dependent porcine coronary arterioles.

Exercise training-enhanced, endothelium-dependent dilation mediated by altered regulation of BK(Ca) channels in collateral-dependent porcine coronary arterioles.
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DOI:
10.1111/micc.12016
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发表时间:
2013-02
期刊:
Microcirculation (New York, N.Y. : 1994)
影响因子:
--
通讯作者:
Heaps CL
Heaps CL
中科院分区:
其他
文献类型:
--
作者:
Xie W;Parker JL;Heaps CL

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检验以下假设:运动训练增加了大电导 Ca2+ 依赖性 K+ (BKCa) 通道对长期闭塞猪心脏侧支依赖性心肌区域内皮介导的冠状动脉扩张的贡献,并且可能在 H2O2 下游发挥作用。将 ameroid 收缩器放置在近端左回旋冠状动脉周围,以诱导尤卡坦小型猪逐渐闭塞。术后八周,猪被随机分配接受静坐或运动训练(跑步机;14 周)方案。与久坐的猪相比,运动训练显着增强了侧支依赖性小动脉(直径约 125 μm)中缓激肽介导的扩张。 BKCa 通道阻滞剂伊贝里奥毒素单独使用或与 H2O2 清除剂聚乙二醇过氧化氢酶联合使用,可以逆转运动训练增强的侧支依赖性小动脉扩张。久坐组和运动训练组的非闭塞小动脉和侧支依赖性小动脉的平滑肌细胞之间,伊比利亚毒素敏感的全细胞 K+ 电流(即 BKCa 通道电流)没有差异。这些数据提供的证据表明,尽管平滑肌 BKCa 通道电流没有变化,但 BKCa 通道活性有助于运动训练增强侧支依赖性冠状动脉内皮依赖性扩张。总而言之,我们的研究结果表明,刺激 BKCa 通道的缓激肽信号通路的一个组成部分可以通过侧支依赖性小动脉的运动训练得到增强,并表明 H2O2 作为介质的潜在作用。
Test the hypothesis that exercise training increases the contribution of large-conductance, Ca2+-dependent K+ (BKCa) channels to endothelium-mediated dilation in coronary arterioles from collateral-dependent myocardial regions of chronically occluded pig hearts and may function downstream of H2O2. An ameroid constrictor was placed around the proximal left circumflex coronary artery to induce gradual occlusion in Yucatan miniature swine. Eight weeks postoperatively, pigs were randomly assigned to sedentary or exercise training (treadmill; 14 wk) regimens. Exercise training significantly enhanced bradykinin-mediated dilation in collateral-dependent arterioles (~125 μm diameter) compared with sedentary pigs. The BKCa-channel blocker, iberiotoxin alone or in combination with the H2O2 scavenger, polyethylene glycol catalase, reversed exercise training-enhanced dilation in collateral-dependent arterioles. Iberiotoxin-sensitive whole-cell K+ currents (i.e., BKCa-channel currents) were not different between smooth muscle cells of nonoccluded and collateral-dependent arterioles of sedentary and exercise trained groups. These data provide evidence that BKCa-channel activity contributes to exercise training-enhanced endothelium-dependent dilation in collateral-dependent coronary arterioles despite no change in smooth muscle BKCa-channel current. Taken together, our findings suggest that a component of the bradykinin signaling pathway, which stimulates BKCa channels, is enhanced by exercise training in collateral-dependent arterioles and suggest a potential role for H2O2 as the mediator.
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