PROACTIVE STAR

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。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。所列机构为中心，不一定是研究者所在机构。本研究将重点关注盐对血压（BP）和下游靶点的肾素-血管紧张素-醛固酮系统（RAAS）以及氧化应激标志物的影响，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的非高血压AA中，高盐诱导氧化应激（通过RAAS的局部血管活化），其在盐敏感（SS）中比在盐抗性（SR）对应物中更大程度地损害NO介导的内皮功能。可以预期，血管紧张素转换酶抑制剂可能是早期干预的目标，以改善血管血流的变化。其他检查将评估基线时和血管紧张素水平调整后的血管功能状态。由于BP本身只能部分解释终末器官对盐的反应，因此还将检查盐敏感性的遗传易感性。具体目标：1）确定非高血压AA中钠平衡急性变化引起血管功能改变的潜在机制，2）将血管终末器官对盐/容量挑战的反应与选定的RAAS和钠转运相关候选基因的多态性变体进行比较。这项精心设计的生理学研究将结合联合收割机对盐和血管紧张素水平的操作以及新的氧化应激标志物，以探测具有终末器官功能障碍风险的非高血压AA受试者这一独特人群的血管/心肾功能。

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.