内皮源性PGI2诱发的血管收缩活动在高血压内皮功能失调中起重要作用。一般认为该收缩反应由TP受体所介导。然而，我们的实验结果提示：PGI2亦有效激活血管平滑肌上的EP3受体，后者与TP受体一同参与该内皮COX产物诱发的血管收缩，或减低其经IP受体诱发的舒张效应。而且我们发现，在高血压大鼠肠系膜动脉分支PGI2经EP3受体诱发的收缩活动显著增强。我们继而设想：高血压可导致EP3受体表达或功能上调，后者进一步加重该病理状况下的内皮功能失调，并对该病的进程产生不利影响。本项目将通过基因敲除小鼠、人体血管及猪冠脉分支、肾内小动脉及高血压模型，结合生理、病理生理、生化及分子生物学方法对上述假说进行验证，以确定EP3受体在正常及高血压内皮的血管调节机能中的作用和机制。预期结果将为明确内皮对血管功能的调控及高血压的病理生理机制提供新的理论基础和实验依据，从而为该病的防治提供优化思路或新的干预靶点信息。

Vasoconstrictor activity derived from endothelial PGI2 plays an important role in the development of endothelial dysfunction under the hypertensive condition. The TP receptor is commonly considered to mediate such a response. Interestingly, our most recent results suggest that PGI2 also effectively activates the EP3 receptor, whose activity along with that of TP causes a vasoconstrictor response to the agonist or reduces the dilator activity induced by the agonist through the IP receptor. Moreover, we found that in spontaneously hypertensive rats the vasoconstrictor activity of PGI2 through the EP3 receptor is increased compared with that of control rats. We thus further propose that hypertension may lead to up-regulation of the expression or function of the EP3 receptor, which would further exacerbate endothelial dysfunction under the disease condition and adversely influence on the pathological development. In this project we will use knockout mice, human vessels，vessels from porcine heart and kidneys, and hypertensive models together with physiological, pathophysiological, biochemical and molecular approaches to test above hypotheses and elucidate the role and underlying mechanisms for the EP3 receptor’s involvement in endothelium-mediated regulation of vascular function both in health and in hypertensive conditions. Our results are expected to uncover novel mechanistic insights into the mechanism of regulation of vascular function by the endothelium and the pathophysiology of hypertension, hence providing novel ideas for optimizing existing therapeutics or yielding new targeting information for the prevention or treatment of the disorder.