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.

本项目的续期申请将跟进家长资助的结果和以前的研究 这表明：1)非裔美国人对压力的利钠反应受损；2)这种模式是 与肾素-血管紧张素-醛固酮系统的功能有关；以及3)与早期 靶器官损害的发展。此外，这些研究还表明，肥胖症的增加有助于 到模式中去。特定的AIMS 1和2将检查血管紧张素受体阻滞剂对 压力诱发压力受损的非裔美国人对应激的压力钠尿反应 利钠，证实血管紧张素II在反应模式中的作用。此外，这一效果将是 比较正常体重和超重个体，假设超重的影响更大 研究对象。目标3将比较血管紧张素受体阻滞剂在携带者和非携带者之间的效果 血管紧张素II受体1型基因的功能多态。这些结果将提供 血管紧张素II机制作用的更多证据和继续我们的基因/环境方法 致力于高血压发病机制的研究。我们的第四个也是最后一个目标是测试 一种假设，在最初的测试中表现出应激诱导的压力性钠尿受损的个体 会表现出更大的血压上升和相关的靶器官损害 正常应激所致的压力性钠尿。这项后续研究将提供更直接的证据 应激性压力性钠尿受损的临床意义。 与公共健康相关：高血压，或称高血压，在中国仍然是一个严重的健康问题 工业化国家。这个问题在非洲裔美国人中尤其明显，他们 “受损”的钠调节起着重要作用。这项研究的结果将有助于进一步界定 遗传易感性和环境胁迫对发育中钠处理的互作效应 高血压，特别是超重的非裔美国人。药物干预也将 为有效管理这一具有潜在临床意义的反应模式提供证据。