PGF2α升高或FP基因表达增加与原发性高血压相关，二者已被认为是治疗高血压相关疾病的新靶点，其在心血管方面调控血压的机制已基本明了，但内源性PGF2α主要来源于肾皮质，其受体FP主要分布在肾皮质远曲小管（DCT），而DCT上ClC-K2（人的ClC-Kb）通道及Na+/Cl-同向转运体（NCC）的活动与机体血压稳定性密切相关。前期研究表明，PGF2α能激活DCT1处唯一钾通道；离体及在体预实验研究发现，PGF2α也能明显激活ClC-K2通道并能上调FP受体及NCC的表达，从而促进NaCl的重吸收。因此，本课题将在此基础上采用膜片钳和分子生物学技术相结合的方法，从离体和在体实验角度，从WT和FP-/-小鼠入手，结合细胞模型，从肾小管离子通道和转运体的视角揭示PGF2α及FP受体升高血压的机制。本项目的完成将进一步完善PGF2α及FP受体参与高血压形成的机制，并为开发高效降压药提供可能靶点。

The increase of PGF2α level or FP gene expression is associated with susceptibility to essential hypertension, and they have been considered to be the new targets for the treatment of hypertension related diseases. The regulation mechanism of blood pressure by PGF2α and FP receptor related to heart and blood vessels has been elucidated, but the endogenous PGF2α mainly comes from renal cortex and its receptor FP is mainly expressed in the cortex distal convoluted tubule (DCT), the activity of ClC-K2 (ClC-Kb in human) channel and Na+/Cl- cotransporter (NCC) is closely related to the stability of blood pressure. Previous studies have shown that PGF2α could stimulate the only functional Kir4.1/5.1 potassium channel in DCT1, and the pre-experimental studies in vitro and in vivo have found that 500nM PGF2α increased the ClC-K2 channel activity and upregulated the abundance of FP receptor, phosphorylated NCC and total NCC, which in turn facilitates the reabsorption of NaCl. Thus, we plan to use patch-clamp and molecular biology technique, from WT to FP-/- mice in vitro and in vivo, and combine with cell model to investigate the modulation mechanism of hypertension induced by PGF2α and FP receptor based on ion channels and transporter in the renal tubule. The completion of this project will further improve the mechanism of PGF2α and FP receptors involved in the formation of hypertension, and provide possible targets to explore the effective antihypertensive agents.