ROLE OF MINERALOCOTICOID RECEPTOR IN OBESITY-RELATED ENDOTHELIAL DYSFUNCTION

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。血流介导的扩张（FMD）反映了血管内皮响应血流的生理增加而产生血管舒张的能力。它主要由血管内皮衍生的一氧化氮的释放介导。在许多类型的心血管疾病（CVD）中，肱动脉FMD减少。肱动脉FMD与冠状动脉血管内皮功能相关，可预测CVD患者未来的心血管事件。FMD在具有高腹内脂肪的个体中也受损，这可能导致这些个体中CVD的患病率增加。因此，明确腹型肥胖患者肱动脉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）诱导的氧化应激在受损的FMD中起着关键作用。由于腹部内脏肥胖也与氧化应激水平和盐皮质激素醛固酮增加有关，因此肥胖患者动脉壁内氧化应激增加的至少一部分可能是由于MR激活导致ROS形成增加，从而导致肥胖相关的FMD下降。因此，本研究的具体目的是测量具有广泛腹部内脏脂肪的男性和女性在用依普利酮进行急性MR阻滞之前和之后的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.