This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor 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.
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