Ethnic Differences in Stress Induced Sodium Regulation & Blood Pressure

本项目的延续申请将跟进家长补助金和以往研究的结果 这表明：1）非洲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; 3）与早期 靶器官损伤的发展。此外，这些研究表明，肥胖症的增加也是导致 模式。具体目标1和2将检查血管紧张素受体阻滞剂对血管紧张素受体的影响。 压力性尿钠排泄对非裔美国人应激反应的影响 尿钠排泄，证实了血管紧张素II在反应模式中的作用。此外，这种影响将 在正常体重与超重个体中进行比较，假设超重 科目目的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作用 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机制作用的额外证据，并继续我们的基因/环境方法 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 假设在最初的测试中显示出受损的压力诱导的压力尿钠排泄的个体 将显示出更大的血压增加和相关的靶器官损害比那些谁显示 正常的压力性尿钠排泄这项后续研究将提供更直接的证据， 压力性尿钠排泄障碍的临床意义 与公共卫生的相关性：高血压，或高血压，仍然是一个重大的健康问题， 工业化国家。这个问题在非洲裔美国人中尤为严重， “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确定 遗传倾向和环境压力对发育过程中钠处理的交互作用 尤其是超重的非裔美国人。药物干预也将 为有效管理这种潜在临床显著应答模式提供证据。

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.