The Role of Signal Transduction Pathways in Hypertension

信号转导途径在高血压中的作用

• 批准号: 7149459
• 负责人: Exazevia M Logan
• 金额: $ 4.19万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-15 至 2008-08-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7149459
• 关键词: angiotensin II; angiotensin receptor; baroreceptors; baroreflex; biological signal transduction; brain metabolism; disease /disorder model; enzyme activity; genetically modified animals; hypertension; laboratory rat; microinjections; mitogen activated protein kinase; neurochemistry; pathologic process; phosphatidylinositol 3 kinase; predoctoral investigator; renin angiotensin system; solitary tract nucleus; sympathetic nervous system

DESCRIPTION (provided by applicant): The goal of the planned research is to either confirm or refute the presence of separate phosphatidylinositol 3 (PI3) and mitogen-activated protein (MAP) kinase pathways in the nucleus tract solitarius (NTS) in various models of hypertension. The overall objective is to investigate the signaling mechanisms at this brain site potentially contributing to development and maintenance of sustained hypertension. Our ongoing studies are designed to provide initial information about the relationship between the apparent enhancement of the sympathetic nervous system in various forms of hypertension and the role of PI3 and MAP kinase signaling pathways in the maintenance of hypertension. Our initial goal is to demonstrate that PI3 and MAP kinase signaling pathways in the NTS of (mRen-2)27 transgenic rats are activated in response to Ang II binding to AT1 receptors. The rationale for the proposed research is that, once knowledge of the mechanisms that are responsible for the development of hypertension has been obtained, it may lead to new strategies that can be used to prevent and/or treat hypertension, thereby reducing the morbidity and mortality associated with high blood pressure.

描述(申请人提供)：计划中的研究的目标是证实或否认在各种高血压模型的孤立核(NTS)中存在不同的磷脂酰肌醇3(PI3)和丝裂原激活蛋白(MAP)激酶通路。总体目标是研究这个大脑部位的信号机制，这些信号机制可能有助于持续性高血压的发展和维持。我们正在进行的研究旨在提供关于各种形式的高血压患者交感神经系统明显增强与PI3和MAPK信号通路在高血压维持中的作用之间的关系的初步信息。我们的初步目标是证明(MREN-2)27只转基因大鼠NTS中的PI3和MAP激酶信号通路在Ang II与AT1受体结合的反应中被激活。这项拟议研究的理由是，一旦了解了导致高血压发展的机制，就可能产生可用于预防和/或治疗高血压的新策略，从而降低与高血压相关的发病率和死亡率。