Impaired flow-dependent control of vascular tone and remodeling in P2X4-deficient mice
Impaired flow-dependent control of vascular tone and remodeling in P2X4-deficient mice
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DOI：
10.1038/nm1338
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发表时间：
2006-01-01
期刊：
影响因子：
82.9
通讯作者：
Ando, J
中科院分区：
文献类型：
--
作者：
Yamamoto, K;Sokabe, T;Ando, J
血管的结构和功能适应环境的变化，如身体发育和运动（1-3）。这种现象是基于内皮细胞感知和响应血流的能力（4-6）;然而，潜在的机制仍不清楚。在这里，我们表明，ATP门控的P2 X4离子通道（7，8），在内皮细胞上表达，并在小鼠中由P2 rx 4编码，在内皮细胞对血流变化的反应中具有关键作用。P2 rx 4（-/-）小鼠没有正常的内皮细胞对流动的反应，例如Ca 2+的内流和随后的有效血管扩张剂一氧化氮（NO）的产生。此外，在P2 rx 4（-/-）小鼠中，由血流量急性增加诱导的血管扩张被显著抑制。此外，与野生型小鼠相比，P2 rx 4（-/-）小鼠的血压更高，尿液中排出的NO产物更少。此外，在P2 rx 4（-/-）小鼠中未观察到适应性血管重塑，即血管尺寸响应于血流的慢性减少而减小。因此，内皮P2 X4通道是至关重要的流量敏感性机制，调节血压和血管重塑。
The structure and function of blood vessels adapt to environmental changes such as physical development and exercise(1-3). This phenomenon is based on the ability of the endothelial cells to sense and respond to blood flow(4-6); however, the underlying mechanisms remain unclear. Here we show that the ATP-gated P2X4 ion channel(7,8), expressed on endothelial cells and encoded by P2rx4 in mice, has a key role in the response of endothelial cells to changes in blood flow. P2rx4(-/-) mice do not have normal endothelial cell responses to flow, such as influx of Ca2+ and subsequent production of the potent vasodilator nitric oxide (NO). Additionally, vessel dilation induced by acute increases in blood flow is markedly suppressed in P2rx4(-/-) mice. Furthermore, P2rx4(-/-) mice have higher blood pressure and excrete smaller amounts of NO products in their urine than do wild-type mice. Moreover, no adaptive vascular remodeling, that is, a decrease in vessel size in response to a chronic decrease in blood flow, was observed in P2rx4(-/-) mice. Thus, endothelial P2X4 channels are crucial to flow-sensitive mechanisms that regulate blood pressure and vascular remodeling.