Intramuscular Mechanisms Regulating Neurocirculatory Control in Chronic Kidney Disease

慢性肾脏病（CKD）患者的体能和运动减少 不容忍，大大降低了与健康有关的生活质量。此外，CKD患者 血压和交感神经系统（SNS）过度升高 在身体活动期间激活，这不仅有助于运动不耐受，而且 与心血管死亡风险增加相关。这种夸张的神经循环 运动期间的反应部分是由于SNS的增强的反射激活， 肌肉传入神经的敏感性增强（即运动加压反射）;然而， 导致CKD患者运动加压反射增强的机制尚不清楚。的 拟议的项目将探讨肌肉增加减少的潜在机制作用， 运动时的间质pH值，以及CKD患者的过度血压反应。 此外，将研究一种新的氨基酸补充方案，作为一种方法， 改善运动血液动力学，增强运动训练对CKD的益处。这些 这些发现将为CKD的运动不耐受特征提供机制性的见解， 并应用实用的药理学和行为疗法来解决这一高度相关的问题， 问题.

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.