PROACTIVE STAR

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这项研究将集中于盐对血压(BP)和肾素-血管紧张素-醛固酮系统(RAAS)下游靶点的影响，以及氧化应激标志物作为一氧化氮(NO)介导的内皮功能受损的潜在机制。我们假设，在遗传易感性的非高血压AA中，高盐诱导氧化应激(通过RAAS的局部血管激活)，对NO介导的内皮功能的损害在盐敏感(SS)组比耐盐(SR)组更大。预计血管紧张素转换酶抑制可能是早期干预以改善血管血流改变的靶点。其他检查将评估基线和血管紧张素水平调整后的血管功能状态。由于BP本身仅部分解释了末端器官对盐的反应，因此也将检查对盐敏感性的遗传易感性。 具体目标：1)明确非高血压AA患者血管功能改变对钠平衡急性变化的潜在机制；2)比较血管末端器官对盐/容量挑战的反应与与RAAS和Na转运相关的候选基因的多态变异。这项精心设计的生理学研究将结合盐和血管紧张素水平的操纵与氧化应激的新标记物，以探索这一独特的非高血压AA患者群体的血管/心脏肾功能。

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. This research will focus on the effect of salt on blood pressure (BP) and downstream targets of the renin-angiotensin-aldosterone system (RAAS) as well as markers of oxidative stress as potential mechanisms underlying impaired nitric oxide (NO)-mediated endothelial function. We hypothesized that in genetically- susceptible non-hypertensive AA, high salt induces oxidative stress (via local vascular activation of RAAS) that impairs NO-mediated endothelial function to a greater extent in salt sensitive (SS) than in salt-resistant (SR) counterparts. It is anticipated that angiotensin-converting enzyme inhibition may represent a target for early intervention to ameliorate the alterations in vascular blood flow. Other examinations will assess the state of vascular function at baseline and after manipulations of angiotensin levels. As BP alone only partially accounts for end-organ responses to salt, genetic susceptibility to salt-sensitivity will be also examined. Specific Aims: 1) define potential mechanisms of alterations in vascular function in response to acute changes in Na balance in non-hypertensive AA and 2) compare the vascular end-organ responses to salt/volume challenges with polymorphic variants of selected candidate genes related to RAAS and Na transport. This carefully designed physiological study will combine manipulations of salt and angiotensin levels with novel markers of oxidative stress to probe vascular/cardiorenal function in this unique population of non-hypertensive AA subjects at risk for end-organ dysfunction.