Pressure-induced constriction is inhibited in a mouse model of reduced betaENaC.
Pressure-induced constriction is inhibited in a mouse model of reduced betaENaC.
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DOI：
10.1152/ajpregu.00212.2009
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发表时间：
2009-06
期刊：
影响因子：
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通讯作者：
Lauren G Vanlandingham;Kimberly P. Gannon;H. Drummond
中科院分区：
文献类型：
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作者：
Lauren G Vanlandingham;Kimberly P. Gannon;H. Drummond
最近的研究表明，某些上皮Na（+）通道（ENaC）蛋白可能是血管平滑肌细胞中机械敏感离子通道复合物的组成部分，有助于压力诱导的大脑中动脉（MCA）收缩。然而，一个特定的ENaC蛋白，β ENaC，在压力诱导的收缩的MCA的作用尚未确定。本研究的目的是确定在β ENaC水平降低的小鼠模型中，压力诱导的MCA收缩是否发生改变。使用定量免疫荧光，我们发现与野生型同窝出生小鼠（+/+）相比，在脑血管平滑肌细胞（VSMCs）中的全细胞betaENaC标记在betaENaC纯合突变（m/m）小鼠中被抑制46%。将来自β ENaC +/+和m/m小鼠的MCA分离并置于血管室中用于肌造影分析。来自betaENaC+/+小鼠的动脉收缩至灌注压逐步增加，并在90 mmHg下发展出10 +/- 2%的最大张力（n = 5）。相比之下，来自betaENaC m/m小鼠的MCA产生显著更少的张力（在90 mmHg下4 +/-1%，n = 5）。不同基因型对KCl（4-80 mM）的血管收缩反应是相同的，对苯丙氨酸（10（-7）-10（-4）M）的反应略有改变，表明VSMC betaENaC水平降低特异性抑制压力诱导的收缩。我们的研究结果表明，betaENaC是所需的正常压力引起的收缩在MCA和提供进一步的支持的假设，betaENaC蛋白质是一个mechanosensor在VSMCs的组件。
Recent studies suggest certain epithelial Na(+) channel (ENaC) proteins may be components of mechanosensitive ion channel complexes in vascular smooth muscle cells that contribute to pressure-induced constriction in middle cerebral arteries (MCA). However, the role of a specific ENaC protein, betaENaC, in pressure-induced constriction of MCAs has not been determined. The goal of this study was to determine whether pressure-induced constriction in the MCA is altered in a mouse model with reduced levels of betaENaC. Using quantitative immunofluorescence, we found whole cell betaENaC labeling in cerebral vascular smooth muscle cells (VSMCs) was suppressed 46% in betaENaC homozygous mutant (m/m) mice compared with wild-type littermates (+/+). MCAs from betaENaC +/+ and m/m mice were isolated and placed in a vessel chamber for myographic analysis. Arteries from betaENaC+/+ mice constricted to stepwise increases in perfusion pressure and developed maximal tone of 10 +/- 2% at 90 mmHg (n = 5). In contrast, MCAs from betaENaC m/m mice developed significantly less tone (4 +/- 1% at 90 mmHg, n = 5). Vasoconstrictor responses to KCl (4-80 mM) were identical between genotypes and responses to phenylephrine (10(-7)-10(-4) M) were marginally altered, suggesting that reduced levels of VSMC betaENaC specifically inhibit pressure-induced constriction. Our findings indicate betaENaC is required for normal pressure-induced constriction in the MCA and provide further support for the hypothesis that betaENaC proteins are components of a mechanosensor in VSMCs.