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的变化，例如身体的发育和锻炼。这种现象是基于内皮细胞（ECs）感知血流和对血流作出反应的能力；然而，其机制尚不清楚。本研究表明，atp门控的P2X4离子通道在ECs上表达，在这一机制中起着关键作用。p2x4缺陷小鼠对血流没有表现出正常的EC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p2x4缺陷小鼠中，由急性血流量增加引起的血管扩张明显受到抑制。此外，与野生型小鼠相比，p2x4缺陷小鼠血压更高，尿液中NO产物的排泄量更少。此外，在p2x4缺陷小鼠中没有观察到适应性血管重塑，即血管大小因慢性血流减少而减小。因此，内皮P2X4通道对于调节血压和血管重构的血流敏感机制至关重要。

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.