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

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切应力或血流的生理性增加而产生血管扩张的能力。它主要由血管内皮细胞衍生的一氧化氮(NO)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也随着年龄的增长而减少，这可能是老年人心血管疾病患病率增加的原因之一。因此，明确臂部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受损中起重要作用。由于年龄的增加也与氧化应激水平的增加有关，因此，随着年龄的增长，动脉壁内氧化应激的增加可能至少部分是由于XO增加了ROS的形成，从而导致了与年龄相关的FMD下降。因此，这项研究的具体目的是在年轻人和老年人久坐不动的情况下，测量用别嘌醇阻断XO氧化酶前后的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 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.