Stress Related Mechanisms of Hypertension Risk

描述(由申请人提供)： 我们PPG的总体目标是更好地了解环境应激、肥胖和钠调节受损在高危人群高血压发病中的协同作用。提出了三个项目，由三个核心(行政、生物分析、生物统计)提供支持。我们提出的三个项目中的每一个都有独特的重点，但它们在各个项目中也有共性。高度的协同和整合使我们能够应用从一个项目获得的信息来理解另一个项目的结果。所有这三个项目都假设SNS诱导的Ang II变化作为功能受损的调解人发挥了核心作用。此外，这三个项目都将侧重于了解压力和肥胖导致非裔美国人高血压的生理机制。项目1和3将研究人类和动物模型中的不同途径。具体地说，项目1假设Ang II是导致非裔美国人压力期间钠滞留的一个因素，这会导致高血压的早期发展。这些研究是由项目3补充的，该项目将重点放在ETB受体和在全身钠滞留方面的使用。项目2将研究早期生活压力对免疫系统中与血管紧张素转换酶相关的功能的影响，以及动物模型中高血压的发展。这激发了项目1在我们的非裔美国人高血压的人类模型中探索这种关系。项目2和项目3都将检查不同肥胖相关疾病模型中与内皮功能相关的因素。总而言之，这些项目之间有很强的协同作用，这些项目将使我们能够确定肥胖和应激相关高血压的关键因素。更重要的是， 它们将使我们能够确定肥胖对应激相关高血压的协同作用的潜在机制。

DESCRIPTION (Provided by applicant): The overall goal of our PPG is to better understand the synergy between environmental stress, adiposity, and impaired sodium regulation in the development of hypertension in high risk populations. Three projects are proposed supported by three Cores (Administrative, Bioassay, Biostatistics). Each of the three projects we propose has a unique focus, but they also have commonalities across the projects. The high synergy and integration allows us to apply information gained from one project to the understanding of the results of another. All three projects hypothesize a central role for SNS-induced changes in Ang II as a mediator of impaired functioning. In addition, all three projects will focus on understanding the physiological mechanisms through which stress and obesity contribute to hypertension in African Americans. Projects 1 and 3 will examine different pathways in human and animal models. Specifically, Project 1 hypothesizes Ang II is one factor responsible for sodium retention during stress in African Americans which leads to the early development of hypertension. These studies are complimented by Project 3 that will focus on the ETB receptor and use in whole body sodium retention. Project 2 will examine the impact of early life stress on Ang H-related functioning of the immune system and the development of hypertension in animal models. This stimulated Project 1 to explore this relationship in our human model of hypertension in African Americans. Projects 2 and 3 will both examine factors related to endothelial function in different models of obesity-related disease. Taken together, there is strong synergy between the projects that will allow us to identify critical factors in obesity and stress-related hypertension. More importantly, they will allow us to identify the mechanisms underlying the synergistic effect of obesity on stress-related hypertension.