Ethnic Differences in Stress Induced Sodium Regulation & Blood Pressure

应激引起的钠调节的种族差异

• 批准号: 7479053
• 负责人: GREGORY ALAN HARSHFIELD
• 金额: $ 34万
• 依托单位: AUGUSTA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7479053
• 关键词: African American; Aldosterone; Angiotensin II; Angiotensin Receptor; Angiotensins; Animal Model; Behavioral; Biochemical; Biochemistry; Biological; Biological Assay; Blood Pressure; Budgets; Cardiac; Cardiovascular system; Data; Developed Countries; Development; Endothelin; Essential Hypertension; Excretory function; Follow-Up Studies; Genes; Genetic; Genetic Polymorphism; Genetic Predisposition to Disease; Genotype; Goals; Health; Heart; High Blood Pressure; Hypertension; Individual; Interdisciplinary Study; Intervention; Kidney; Left Ventricular Mass; Manuscripts; Measurement; Natriuresis; Nitric Oxide; Obesity; Organ; Overweight; Oxidative Stress; Pattern; Play; Population; Potassium; Predisposition; Preparation; Principal Investigator; Process; Psyche structure; Public Health; Receptor, Angiotensin, Type 1; Regulation; Relative (related person); Renin; Renin-Angiotensin-Aldosterone System; Research; Rest; Role; Services; Sodium; Stress; Structure; System; Testing; Theoretical model; Weight; Work; blood pressure regulation; clinically significant; data management; ethnic difference; follow-up; gene environment interaction; human subject; improved; parent grant; pressure; programs; response; saluretic; statistics

The renewal application for this project will follow-up the findings of the parent grant and previous studies which suggest: 1) African-Americans have an impaired natriuretic response to stress; 2) this pattern is related to the functioning of the renin-angiotensin-aldosterone system; and 3) is associated with the early development of target organ damage. In addition, these studies 4) indicate increased adiposity contributes to the pattern. Specific Aims 1 and 2 will examine the effects of an angiotensin receptor blocker on the pressure natriuresis response to stress in African-Americans with impaired stress-induced pressure natriuresis, confirming the role of angiotensin II in the response pattern. Furthermore, this effect will be compared in normal weight versus overweight individuals, with a hypothesized greater effect in overweight subjects. Aim 3 will compare the effects of an angiotensin receptor blocker between carriers and noncarriers of a functional polymorphism of the angiotensin II receptor type 1 gene. These results will provide additional evidence for the mechanistic role of angiotensin II and continue our gene/environmental approach to the study of mechanisms underlying the development of hypertension. Our fourth and final aim is to test the hypothesis that individuals who displayed impaired stress-induced pressure natriuresis on initial testing will display greater increases in blood pressure and related target organ damage than those who displayed normal stress-induced pressure natriuresis. This follow-up study will provide more direct evidence of the clinical significance of impaired stress-induced pressure natriuresis. Relevance to public health: High blood pressure, or hypertension, remains a significant health problem in industrialized nations. The problem is particularly significant in the African-American population in whom "impaired" sodium regulation plays an important role. The results of this study will help further define the interactive effects of genetic predisposition and environmental stress on sodium handling in the development of hypertension, particularly in overweight African-Americans. The pharmacologic interventions will also provide evidence for effective management of this potentially clinically significant response pattern.

该项目的续签申请将跟进父母赠款和以前的研究的结果 这表明：1）非裔美国人对压力的纳地尿反应受损； 2）这种模式是 与肾素 - 血管紧张素 - 醛固酮系统的功能有关； 3）与早期有关 发展目标器官损伤。此外，这些研究4）表明肥胖增加有助于 到图案。具体目的1和2将检查血管紧张素受体阻滞剂对 压力源自压力的压力反应对压力诱导的非裔美国人的压力反应 Natriuresis，证实了血管紧张素II在反应模式中的作用。此外，这种效果将是 比较正常体重与超重个体，假设超重的影响更大 主题。 AIM 3将比较载体和非载体之间血管紧张素受体阻滞剂的影响 血管紧张素II受体1型基因的功能多态性。这些结果将提供 血管紧张素II的机理作用的其他证据，并继续我们的基因/环境方法 研究高血压发展的基础机制。我们的第四个也是最后一个目标是测试 在初始测试时表现出压力诱导的压力纳地尿的个人的假设 与展示的人相比，血压和相关目标器官损害的升高会更大 正常应力诱导的压力纳地尿液。这项后续研究将提供更多直接的证据 压力诱导的压力纳地尿症受损的临床意义。 与公共卫生有关：高血压或高血压仍然是一个重大健康问题 工业化国家。这个问题在非裔美国人人口中尤其重要 “受损”钠调节起着重要作用。这项研究的结果将有助于进一步定义 遗传易感性和环境压力对钠处理的交互作用 高血压，特别是在超重的非裔美国人中。药理学干预措施也将 提供有效管理这种潜在临床意义的反应模式的证据。