MOREHOUSE CCRE DP3- SALT AND VASCULAR FUNC IN NON-HYPERTENSIVE AFRICAN AMERICANS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 早期识别非洲裔美国人（AA）高血压（HTN）的风险可能会提供一个机会，以防止疾病的进展。一种感兴趣的HTN相关中间表型是对盐和水稳态变化的可变血压（BP）响应。这种对BP的盐敏感性（SS）可能是遗传决定的，因为超过50%的高血压AA是NaCl敏感的，并且具有更大的发展高血压靶器官损伤的倾向。本项目的主要目的是表征在遗传易感的非高血压AA中，血管和心肾功能对盐摄入的生理改变，并评估介导这些终末器官对盐的反应的潜在病理生物学途径。我们的假设是高盐/低钾饮食，典型的AA，抑制经典的循环肾素血管紧张素-醛固酮系统（RAAS），但激活组织血管紧张素-醛固酮系统。当地 组织隔室中血管紧张素和醛固酮的产生促进活性氧物质的产生，活性氧物质损害一氧化氮（NO）介导的血管舒张功能。据推测，这种内皮功能的损害通过盐诱导的BP升高以外的机制导致血管功能障碍和对亚临床终末器官功能障碍的早期发展的易感性增加;然而，仔细表征盐对BP和RAAS下游靶标的影响的尝试有限，氧化应激循环标志物作为非高血压AA实质性样本中内皮功能受损的潜在决定因素。我们提出了仔细的生理实验，将结合联合收割机操纵血管紧张素水平和新的氧化应激和血管功能的标志物在非HTN AA的终末器官功能障碍的风险。拟议的项目将是第一个系统地确定盐摄入量变化对这些特定的早期影响的项目之一。 血管和心/肾功能的标志物，并在这一独特的基于人群的健康受试者样本中表征这种反应的影响。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Early identification of African Americans (AA) at risk for hypertension (HTN) may provide an opportunity to prevent progression of the disease. One HTN-related intermediate phenotype of interest is the variable blood pressure (BP) response to changes in salt and'water homeostasis. This salt-sensitivity (SS) to BP may be genetically determined as over 50% of hypertensive AA are NaCI-sensitive and have a greater propensity to develop hypertensive target-organ damage. The -main objective of this project is to characterize physiologic alterations in vascular and cardio-renal function in response to salt intake in genetically susceptible non-hypertensive AA and to assess the potential pathobiological pathways mediating these end-organ responses to salt. Our hypothesis is that a high salt/low potassium diet, typical of AA, inhibits the classic circulating reninangiotensin- aldosterone system (RAAS) but activates the tissue angiotensin-aldosterone system. The local generation of angiotensin and aldosterone within tissue compartments promotes the generation of reactive oxygen species that impairs nitric oxide (NO)-mediated vasodilatory function. It is postulated that this impairment in endothelial function contributes to vascular dysfunction and increased susceptibility to the early development of sub-clinical end-organ dysfunction, by mechanisms additional to the salt-induced rise in BP; However, there have been limited attempts to carefully characterize the effects of salt on BP and downstream targets of the RAAS, circulating markers of oxidative stress as potential determinants of impaired endothelial function in a substantive sample of non-hypertensive AA. We propose careful physiologic experiments that will combine manipulations of angiotensin levels and novel marker of oxidative stress and vascular function in non-HTN AA at risk for end-organ dysfunction. The proposed project will be among the first to systematically define the early influence of variations in salt intake on these specific markers of vascular and cardiac/renal function and to characterize the effect of this response in this unique population-based sample of otherwise healthy subjects.