Intramuscular Mechanisms Regulating Neurocirculatory Control in Chronic Kidney Disease

点击翻译按钮获取中文摘要

Chronic Kidney Disease (CKD) patients have reduced physical capacity and exercise intolerance that significantly decrease health-related quality of life. In addition, CKD patients exhibit an exaggerated increase in blood pressure and sympathetic nervous system (SNS) activation during physical activity, which not only contributes to exercise intolerance, but is also associated with an increased risk of cardiovascular mortality. This exaggerated neurocirculatory response during exercise is due, in part, to an enhanced reflex activation of the SNS via heightened sensitization of muscle afferent nerves (i.e. exercise pressor reflex); however, the mechanisms leading to the exaggerated exercise pressor reflex in CKD remain unknown. The proposed project will explore the potential mechanistic role of augmented decreases in muscle interstitial pH with exercise, and the exaggerated blood pressure response in CKD. Furthermore, a novel amino acid supplementation regimen will be investigated as a method to improve exercise hemodynamics and enhance the benefits of exercise training in CKD. These findings will provide mechanistic insights into the exercise intolerance that characterizes CKD, and also apply a practical pharmacologic and behavioral therapy to address this highly relevant problem.