Exercise and Vascular Function in Chronic Kidney Disease

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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.