ROLE OF XANTHINE OXIDASE IN THE AGE-RELATED DECLINE IN FLOW-MEDIATED DILATION

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于剪切应力或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（NO）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也随着年龄的增长而减少，这可能导致老年人CVD患病率增加。因此，确定肱FMD随年龄增长而受损的机制具有重要的临床意义。 实验证据表明，黄嘌呤氧化酶（XO）诱导的氧化应激在心血管疾病患者FMD受损中起关键作用。由于年龄增长也与氧化应激水平增加有关，因此随着年龄的增长，动脉壁内氧化应激增加的至少一部分可能是由于XO形成的ROS增加，导致FMD与年龄相关的下降。因此，本研究的具体目的是测量FMD之前和之后XO氧化酶阻断别嘌呤醇在年轻和老年久坐的成年人。

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.