Sympathetic hyperactivity in end-stage renal disease

描述（由申请人提供）：终末期肾病（ESRD）患者的心血管死亡率极高。ESRD患者有高基线交感神经系统（SNS）活动，这有助于增加心血管死亡率和高血压。该项目的目的是阐明该人群中SNS激活的机制，并开发改善SNS过度活跃的治疗方法，从而降低心血管疾病死亡率。假设是肌肉调节会增加ESRD患者的SNS活动，运动训练可能会改善这些患者的SNS活动和血压。第一个目的是确定ESRD受试者是否表现出异常的骨骼肌反射激活SNS活动导致整体SNS过度活跃。具体来说，代谢受体激活的减弱和机械受体激活的增强在ESRD中是预期的。将比较ESRD受试者和对照组的SNS流出量，同时进行手臂任务以刺激机械受体和代谢受体。第二个目的是确定分析性运动训练是否能改善ESRD患者的基线SNS多动和动态血压模式。如果ESRD患者的肌肉反射激活发生改变，我们还将确定运动训练是否能恢复这些患者的代谢受体敏感性并降低机械受体敏感性。ESRD受试者将被随机分配到每周三次的透析内运动方案和静止不动方案，并评估这种干预对SNS多动、动态血压模式和正常肌肉力学恢复的影响。如果发现溶栓性运动训练是有益的，这种可行的非药物干预可能成为降低ESRD人群心血管发病率和死亡率的一种制度性治疗方法。本研究项目的目的是发现血液透析肾衰竭患者心脏病死亡率高的原因。在肾衰竭患者中，缺乏运动可能会引起肌肉反射异常，导致肾上腺素释放增加和血压升高，从而导致心脏病。因此，血液透析期间的有氧运动可以改善身体状况，降低血压和肾上腺素释放，从而降低肾衰竭患者死于心脏病的风险。

DESCRIPTION (provided by applicant): Patients with end-stage renal disease (ESRD) suffer from an exceedingly high rate of cardiovascular mortality. ESRD patients have high baseline sympathetic nervous system (SNS) activity which contributes to their increased cardiovascular mortality and high blood pressure. The objective of this project is to elucidate mechanisms of SNS activation in this population, and develop therapies to ameliorate SNS hyperactivity and thereby decrease cardiovascular mortality. The hypothesis is that muscle deconditioning increases SNS activity in ESRD, and that exercise training may improve SNS activity and BP in these patients. The first aim is to determine if ESRD subjects exhibit abnormal skeletal muscle reflex activation of SNS activity leading to overall SNS hyperactivity. Specifically, blunting of metaboreceptor activation and augmentation of mechanoreceptor activation is expected in ESRD. SNS outflow will be compared between ESRD subjects and controls while arm tasks are performed to stimulate mechanoreceptors and metaboreceptors. The second aim is to determine if intradialytic exercise training improves baseline SNS hyperactivity and ambulatory blood pressure patterns in ESRD. If there is altered muscle reflex activation in patients with ESRD, we will also determine if exercise training restores metaboreceptor sensitivity and decreases mechanoreceptor sensitivity in these patients. ESRD subjects will be randomized to a thrice- weekly exercise intradialytic regimen versus remaining sedentary, and the effects of this intervention on SNS hyperactivity, ambulatory blood pressure patterns, and restoration of normal muscle mechanics, will be assessed. If intradialytic exercise training is found to be beneficial, this feasible, nonpharmacologic intervention may become an instituted therapy to decrease cardiovascular morbidity and mortality in the ESRD population. The goal of this research project is to discover causes for the high rate of death from heart disease in patients with kidney failure on hemodialysis. In patients with kidney failure, physical inactivity may contribute to heart disease by causing abnormal muscle reflexes that lead to increased adrenaline release and blood pressure. Therefore, aerobic exercise during hemodialysis may improve physical conditioning and decrease blood pressure and adrenaline release, thereby ameliorating the risk of death from heart disease in patients with kidney failure.