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，在美国有2000多万成年人受到影响。除了进展为肾功能衰竭的风险外，慢性肾脏病还与心血管疾病(CVD)的患病率增加有关，而传统的危险因素无法完全解释这一点。内皮功能受损是动脉粥样硬化和心血管疾病发展过程中的主要事件，其并发症是CKD发病和死亡的最重要原因。慢性肾脏病患者和血液透析患者的氧化应激水平升高，似乎会损害内皮功能。因此，氧化应激继发的内皮功能障碍可能导致CKD患者肾功能恶化和心血管风险增加。为了改善这些患者的肾脏和心血管预后，需要旨在恢复CKD患者血管功能的干预措施。有氧运动训练已被证明可以减轻氧化应激和改善血管功能，可能是慢性肾脏病的一种有效的辅助治疗策略，但其在慢性肾脏病中的应用尚未得到研究。本研究旨在探讨有氧运动训练对慢性肾脏病微血管和导管动脉内皮细胞功能的影响。我们特别假设运动训练将改善一氧化氮介导的皮肤血管扩张和肱动脉内皮依赖性扩张。我们还假设氧化应激将会减少，运动训练后局部注射抗坏血酸不会影响皮肤血管扩张。将获得内皮细胞，以评估运动训练对血管的影响 内皮细胞氧化应激及相关分子机制。CKD患者将随机分为12周的有氧运动训练或控制期。血管内皮依赖性扩张和局部加热引起的皮肤血管扩张将使用激光多普勒血流测定仪进行评估，前臂皮内微透析将用于评估微血管系统。对局部加热反应的皮肤血管扩张将在Ringers(对照)站点、L命名的站点(以评估NO的贡献)和抗坏血酸站点(以评估氧化应激的作用)进行评估。这些措施将在基线和12周内进行。这一全面的内皮细胞评估将使我们能够明确确定运动训练是否改善了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.