VASCULAR RESPONSES IN TRANSGENIC HYPERTENSIVE MICE

转基因高血压小鼠的血管反应

• 批准号: 6013025
• 负责人: SEAN P DIDION
• 金额: $ 3.17万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-01-15 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6013025
• 关键词: aorta; blood pressure; blood vessel disorder; cellular pathology; disease /disorder model; enzyme activity; gene expression; genetic strain; genetically modified animals; hypertension; laboratory mouse; muscle contraction; nitric oxide; polymerase chain reaction; renin angiotensin system; superoxide dismutase; superoxides; vascular endothelium; vascular smooth muscle

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.

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可能是血管中活性氧产生的重要刺激物。虽然高血压与血管功能障碍有关，但与这些变化相关的细胞和分子机制的再分级知之甚少。本提案中概述的研究将使用两种新型高血压小鼠模型（全身模型，R+/A+和肾脏特异性模型，R+/KA+）。将检查的具体目的是：1）检查全身模型和肾脏特异性模型中存在血管功能障碍的假设。预计与肾特异性模型相比，系统模型中的功能障碍水平将更高，即使两种菌株的动脉压相似。2)在两种高血压模型中，检验血管壁内超氧化物水平升高的假设。预计在全身模型中，可以使NO还原的超氧化物的水平将更高。