Exercise and Vascular Function in Chronic Kidney Disease

描述（由申请人提供）：慢性肾脏病（CKD）是一个主要的公共卫生问题，影响美国2000多万成年人。除了进展为肾衰竭的风险外，CKD还与心血管疾病（CVD）患病率增加相关，这无法通过传统风险因素完全解释。内皮功能受损是动脉粥样硬化和CVD发展的主要事件，其并发症是CKD发病率和死亡率的最重要原因。CKD患者和血液透析患者的氧化应激水平升高，似乎损害了内皮功能。因此，继发于氧化应激的内皮功能障碍可能导致CKD患者的肾功能恶化和CVD风险增加。需要旨在恢复CKD患者血管功能的干预措施来改善这些患者的肾脏和心血管结局。有氧运动训练已被证明可以减少氧化应激和改善血管功能，可能是CKD的有效辅助治疗策略，但其在CKD中的应用尚未研究。本研究旨在探讨有氧运动训练对慢性肾脏病患者微血管及导管动脉内皮功能的影响。我们特别假设，运动训练将改善一氧化氮介导的皮肤血管舒张和肱动脉内皮依赖性舒张。我们还假设，氧化应激将减少，皮肤血管舒张将不受局部抗坏血酸输注后运动训练。取内皮细胞，观察运动训练对血管内皮细胞的影响。 内皮细胞氧化应激及相关分子机制。CKD患者将随机分配至12周有氧运动训练或对照期。肱动脉的血流介导扩张将用于评估导管内皮依赖性扩张和皮肤血管舒张，以响应使用激光多普勒血流仪的局部加热，并将在前臂中评估皮内微透析以评价微血管系统。将在林格氏（对照）部位、L-NAME部位（评估NO贡献）和抗坏血酸部位（评估氧化应激的作用）评估局部加热引起的皮肤血管舒张。这些测量将在基线和12周时进行。这项全面的内皮评估将使我们能够明确确定运动训练是否改善CKD患者的血管健康。

DESCRIPTION (provided by applicant): Chronic kidney disease (CKD) is a major Public Health problem affecting more than 20 million adults in the United States. In addition to the risk of progressing to renal failure, CKD is associated with an increased prevalence of cardiovascular disease (CVD) that is not fully explained by traditional risk factors. Impaired endothelial function is a primary event in the development of atherosclerosis and CVD and its complications are the most important cause of morbidity and mortality in CKD. Oxidative stress is elevated in patients with CKD and those on hemodialysis and appears to impair endothelial function. Thus, endothelial dysfunction secondary to oxidative stress may cause renal function to deteriorate and CVD risk to increase in CKD. Interventions designed to restore vascular function in CKD are required to improve renal and cardiovascular outcomes in these patients. Aerobic exercise training has been shown to reduce oxidative stress and improve vascular function and may be an effective adjunct therapeutic strategy in CKD however its use in CKD has yet to be investigated. We propose to investigate the effects of aerobic exercise training on microvascular and conduit artery endothelial function in CKD. We specifically hypothesize that exercise training will improve nitric oxide mediated cutaneous vasodilation and brachial artery endothelial-dependent dilation. We also hypothesize that oxidative stress will be reduced, and that cutaneous vasodilation will be unaffected by local ascorbic acid infusion following exercise training. Endothelial cells will be obtained to assess the effects of exercise training on vascular endothelial cell oxidative stress and related molecular mechanisms. CKD patients will randomized to either 12 weeks of aerobic exercise training or control period. Flow mediated dilation of the brachial artery will be used to assess conduit endothelial-dependent dilation and cutaneous vasodilation in response to local heating using laser Doppler flowmetry and intradermal microdialysis will be assessed in the forearm to evaluate the microvasculature. Cutaneous vasodilation in response to local heating will be assessed at a Ringers (control) site, L-NAME site (to assess the NO contribution), and an ascorbic acid site (to assess the role of oxidative stress). These measures will be at baseline and 12 weeks. This comprehensive endothelial assessment in will allow us to definitively determine if exercise training improves vascular health in patients with CKD.