Ang-(1-7)调控高血压大鼠血管功能的作用和机制研究

The decreased vascular relaxation and enhanced vascular tension which contribute to an increase in total peripheral resistance are important characteristics of hypertension. Our previous studies have found that central angiotensin-(1-7) (Ang-(1-7)) plays an important role in modulating blood pressure in hypertensive rats. A preliminary study in our lab has found that peripheral intravenous injection of Ang-(1-7) decreased blood pressure in hypertensive rats. However the effects of Ang-(1-7) on enhanced vascular tension and decreased vascular relaxation in hypertension remains unclear. Based on our previous findings, we are going to investigate the role and mechanism of Ang-(1-7) on the vasoconstrictor and vasodilatation function in hypertensive rats at integrative, cellular, molecular and gene expression levels in vitro and in vivo. This project is also designed to investigate the interaction between Ang-(1-7) and Ang II on modulating vascular function and to observe whether chronic application of Ang-(1-7) could improve hypertension. It is hopeful to provide a novel approach and an experimental foundation for treating hypertension.

高血压时小动脉舒张能力下降，血管张力增加，外周阻力持续升高，是高血压的重要特征。我们前期的研究发现中枢血管紧张素-（1-7）[Ang-(1-7)]在血压调节中起重要作用。目前我们在高血压大鼠外周静脉注射Ang-(1-7)初步显示其降低血压的效果，但其对高血压增强的血管收缩功能和降低的血管舒张功能的影响和机制尚不清楚。本项目以既往研究发现为基础，应用多种先进研究方法，从整体、细胞和分子基因水平综合研究Ang-(1-7)在高血压大鼠冠状动脉和肺动脉收缩功能和舒张功能中的调节作用及其作用机制，以及在这过程中其与Ang II的交互作用，并通过慢性实验增强Ang-(1-7)活动观察是否对高血压起到改善作用。该研究结果不仅有助于我们继续阐明Ang-(1-7)与高血压发病机制的关系这一重大理论问题，而且为高血压病的防治提供新思路、新靶点和奠定实验基础。

高血压时小动脉舒张能力下降，血管张力增加，外周阻力持续升高，是高血压的重要特征。我们前期的研究发现中枢血管紧张素-（1-7）[Ang-(1-7)]在血压调节中起重要作用。通过4年的研究，我们得到的结果表明高血压时动脉内皮功能障碍，Ang-(1-7)在外周血液循环中具有直接舒张血管、改善高血压内皮功能、拮抗Ang II的效应、降低血压的效应，NO-cGMP-PKG信号通路介导Ang-(1-7)的这一系列效应。高血压大鼠血液中Ang-(1-7)/Mas受体活动的下降可能是导致高血压的重要原因。这些提示我们，增强血液循环中Ang-(1-7)/ Mas受体活动可能具有对抗高血压的作用，对高血压的改善提供了新思路和新药靶点。该研究结果不仅有助于我们继续阐明Ang-(1-7)与高血压发病机制的关系这一重大理论问题，而且为高血压病的防治提供新思路、新靶点和奠定实验基础。