目前，普遍认为内皮PGI2合成具有血管舒张作用。然而，我们研究结果显示：COX-1主导的内皮PGI2合成诱发TP受体介导的血管收缩。结合我们最新实验结果，申请人首次提出：TP与IP受体同时参与PGI2的血管收缩性调控，其中IP受体的功能或表达差异是内皮COX-1激活在不同血管诱发收缩或舒张效应的主要原因。而且，我们结果提示，内皮PGI2合成可诱发肾动脉血管收缩。由于高血压合并内皮功能失调，且肾动脉在血压调节中起着关键作用，我们进一步设想：内皮PGI2的血管收缩作用可加重肾动脉内皮功能失调，从而对高血压的发生与发展产生不利影响。因此，本项目将通过基因剔除小鼠、人体血管、及高血压模型验证以上假说，以确定内皮PGI2合成对血管收缩性能及肾血流的调控、及其在高血压病中的作用和机制。预期研究结果将为血管收缩性能的调控、以及高血压的病理生理机制提供新的理论及实验依据，从而为该病的防治提供新的靶点信息。

Endothelial PGI2 synthesis is generally considered to be vasodilatory. However, our results showed that endothelial COX-1-derived PGI2 evoked TP receptor-mediated vasoconstriction. On the basis of this together with our recent findings, we hypothesized that both TP and IP receptors are concomittantly involved in the control of vasomotor reaction mediated by the endothelial PGI2 synthesis, and the varied expression or functional presence of IP receptors is the major reason for the vasried vasoconstrictor or dilator effect evoked by endothelial COX-1 activation among different vascular beds. Moreover, our results suggest that endothelial PGI2 synthesis also evokes renal vasoconstriction. Given the commonness of endothelial dysfuction associated with hypertension and the critical role of renal vasculature in regulating systemic blood pressure, we further proposed that the vasoconstrictor effect of endothelial PGI2 synthesis could add to the renal endothelial dysfunction, and hence adversely affect the development of hypertension. Therefore, this project will use genetically altered mice，human vessels, and hypertensive mouse or rat models to substantaite our above hypotheses, and our results are expected to uncover novel mechanistic insights into endothelium-mediated regulation of vasomotor function and the pathophysiology of hypertension, which could provide new targeting information for the prevention or treatment of the disease.