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 shear stress or blood flow. It is primarily mediated by the release of vascular endothelial derived nitric oxide (NO). 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 also decreases with age, which may contribute to the increased prevalence of CVD in older adults. Therefore, identifying the mechanisms involved in the impairment of brachial FMD with age has important clinical implications. Experimental evidence sugessts that xanthine oxidase (XO) induced oxidative stress plays a critical role in impaired FMD in patients with cardiovascular diseases. Because advancing age is also associated with increased oxidative stress level, it is possible that at least part of the increased oxidative stress within the arterial wall seen with age may be due to an increased formation of ROS by XO, contributing to the age-related decline in FMD. Consequently, the specific aim of this study is to measure FMD before and after XO oxidase blockade with allopurinol in young and older sedentary adults.
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