VASCULAR RESPONSES IN TRANSGENIC HYPERTENSIVE

多年来，人们已经知道肾素-血管紧张素系统对某些形式的高血压有重要作用。一些研究表明，血管紧张素II可能是血管内产生活性氧的重要刺激因素。尽管已知高血压与血管功能障碍有关，但对与这些变化相关的细胞和分子机制的再评估知之甚少。这项建议中概述的研究将使用两种新的小鼠高血压模型(全身性模型，R/A和肾脏特异性模型，R/KA)。将检验的具体目的是为了检验系统模型和肾脏特有模型中存在血管功能障碍的假说(L)。预计与肾脏特异性模型相比，系统模型中的功能障碍程度会更大，即使两个品系的动脉压相似。2)验证两种高血压模型中血管壁超氧化物水平升高的假说。预计在系统模型中，可以使NO失活的超氧化物水平将更高。

It has been know for many years that the renin-angiotensin system contributes importantly to some forms of hypertension. Some studies suggest that angiotensin II may be an important stimulus for generation of reactive oxygen species in blood vessels. Although hypertension is known to be associated with vascular dysfunction, little is known regrading cellular and molecular mechanisms that are associated with these changes. The studies outlined in this proposal will use two novel murine models of hypertension (systemic model, R+/A+ and renal-specific model, R+/KA+). The Specific Aims that will be examined are l) to examine the hypothesis that vascular dysfunction is present in the systemic model and renal- specific model. It is anticipated that the level of dysfunction will be greater in the systemic model as compared to the renal- specific model even though arterial pressure is similar in the two strains. 2) To examine the hypothesis that superoxide levels are enhanced within the vascular wall in the two models of hypertension. It is anticipated that levels of superoxide, which can inactivate NO, will be greater in the systemic model.