Generating blood-flow-sensing-molecule-deficient mice and analysis of their physiological functions

血管的结构和功能会适应环境变化，例如身体发育和运动。这种现象是基于内皮细胞（EC）感知和响应血流的能力;然而，其机制仍不清楚。在这里，我们表明，ATP门控P2 X4离子通道，表达在EC上，是一个关键的球员的机制。P2 X4缺陷小鼠不表现出正常的EC对血流的反应，如Ca^2+内流和随后产生的一氧化氮（NO），一种有效的血管扩张剂。此外，在P2 X4缺陷小鼠中，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 X4缺陷型小鼠的血压更高，尿液中排出的NO产物更少。此外，没有适应性血管重塑，即，在P2 X4缺陷小鼠中观察到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, for example, physical development and exercise. This phenomenon is based on the ability of the endothelial cells (ECs) to sense and respond to blood flow; however, its mechanism remains unclear. Here we show that ATP-gated P2X4 ion channel, expressed on ECs, is a key player in the mechanism. P2X4-deficient mice do not exhibit normal EC responses to flow, such as Ca^<2+> influx and subsequent production of nitric oxide (NO), a potent vasodilator. Additionally, vessel dilation induced by acute increases in blood flow is markedly suppressed in P2X4-deficient mice. Furthermore, P2X4-deficient mice have higher blood pressure and excrete smaller amounts of NO products in their urine than wild-type mice. Moreover, no adaptive vascular remodeling, i.e., decreases in vessel size in response to chronic decrease in blood flow, is observed in the P2X4-deficient mice. Thus, endothelial P2X4 channels are critical to the flow-sensitive mechanisms that regulate blood pressure and vascular remodeling.