Sympathetic hyperactivity in end-stage renal disease

描述(申请人提供)：终末期肾病(ESRD)患者心血管死亡率极高。终末期肾病患者具有高基线交感神经系统(SNS)活动，这是导致他们心血管死亡率和高血压增加的原因之一。本项目的目的是阐明SNS在这一人群中激活的机制，并开发治疗方法来改善SNS过度活动，从而降低心血管死亡率。假说是，肌肉去条件反射增加了终末期肾病的SNS活性，运动训练可能会改善这些患者的SNS活性和血压。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的SNS活动，从而导致整体SNS多动。具体地说，在ESRD中，代谢物受体激活的钝化和机械感受器激活的增强是可望的。在执行ARM任务以刺激机械感受器和代谢物感受器时，将比较ESRD受试者和对照组之间的SNS流出。第二个目的是确定传统运动训练是否能改善终末期肾病患者的基础SNS、多动症和动态血压模式。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恢复了这些患者的代谢物感受器敏感性并降低了机械感受器敏感性。ESRD受试者将被随机分成传统透析方案中每周三次的锻炼方案和保持久坐不动的方案，并将评估这种干预对SNS多动、动态血压模式和恢复正常肌肉力学的影响。如果传统的运动训练被发现是有益的，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既定疗法。这项研究项目的目标是找出血液透析中肾功能衰竭患者心脏病死亡率高的原因。在肾衰竭患者中，缺乏运动可能会导致肌肉反射异常，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.