ROLE OF MINERALOCOTICOID RECEPTOR IN OBESITY-RELATED ENDOTHELIAL DYSFUNCTION

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。血流介导的扩张(FMD)反映了血管内皮细胞对生理性血流增加产生血管扩张的能力。它主要由血管内皮细胞来源的一氧化氮的释放所介导。在许多类型的心血管疾病(CVD)中，臂部FMD降低。臂部FMD与冠状动脉血管内皮功能相关，并可预测心血管疾病患者未来的心血管事件。FMD在腹内脂肪含量高的个体中也会受损，这可能是导致这些个体心血管疾病患病率增加的原因之一。因此，明确腹内型肥胖导致的臂部FMD受损的机制具有重要的临床意义。实验证据表明，盐皮质激素受体(MR)诱导的氧化应激在FMD受损中起关键作用。由于腹部内脏肥胖还与氧化应激水平和矿化皮质醇醛固酮增加有关，肥胖症患者动脉壁内氧化应激增加的至少部分原因可能是由于MR的激活增加了ROS的形成，从而导致肥胖相关的FMD下降。因此，这项研究的具体目的是测量Eplerenone急性MR阻断前后腹部内脏脂肪范围广泛的男性和女性的FMD。

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. Flow-mediated dilation (FMD) reflects the ability of the vascular endothelium to produce vasodilation in response to physiological increases in blood flow. It is primarily mediated by the release of vascular endothelium derived nitric oxide. Brachial FMD is reduced in many types of cardiovascular diseases (CVD). Brachial FMD correlates with coronary vascular endothelial function and predicts future cardiovascular events in patients with CVD. FMD is also impaired in individuals with high intra-abdominal fat, which may contribute to the increased prevalence of CVD in these individuals. Therefore, identifying the mechanisms involved in the impairment of brachial FMD with abdominal visceral obesity has important clinical implications. Experimental evidence suggests that mineralocorticoid receptor (MR)-induced oxidative stress plays a critical role in impaired FMD. Because abdominal visceral obesity is also associated with increased oxidative stress levels and the mineralocorticoid aldosterone, it is possible that at least part of the increased oxidative stress within the arterial wall seen with obesity may be due to an increased formation of ROS by the activation of MR, contributing to the obesity-related decline in FMD. Consequently, the specific aim of this study is to measure FMD before and after acute MR blockade with Eplerenone in men and women with a broad range of abdominal visceral fat.