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Intramuscular Mechanisms Regulating Neurocirculatory Control in Chronic Kidney Disease

慢性肾病神经循环控制的肌内调节机制

基本信息

批准号：
9758645
负责人：
Justin Daniel Sprick
金额：
$ 6.12万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-07-01 至 2021-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9758645
关键词：
Acidosis Acids Address Aerobic Exercise Amino Acids Attenuated Behavior Therapy Bicarbonates Biological Availability Blood Pressure Buffers Carnosine Chronic Kidney Failure Clinical Clinical Trials Development Discipline Elderly Environment Event Exercise Exercise Tolerance Exhibits Funding Health Histidine Human Imaging Techniques Intramuscular Investigation Ions Knowledge Link Magnetic Resonance Spectroscopy Masks Measures Mediating Mentors Metabolic acidosis Methods Moderate Exercise Muscle Muscle Fatigue Myalgia Near-Infrared Spectroscopy Nerve Endings Oral Parents Pathology Patients Pharmacology Physical Capacity Physical Exercise Physical Function Physical activity Physiology Placebos Play Protons Quality of life Randomized Reflex action Regimen Research Risk Role Safety Stretching Supplementation Sympathetic Nervous System Testing Therapeutic Intervention Translating Treatment Efficacy afferent nerve beta-Alanine cardiovascular risk factor clinical application cost design dietary supplements exercise capacity exercise intolerance exercise training experimental study health related quality of life hemodynamics improved in vivo innovation insight interstitial mortality muscle metabolism novel nutritional supplementation patient population response skills

项目摘要

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.

慢性肾脏病 (CKD) 患者的体力和运动能力下降不耐受会显着降低与健康相关的生活质量。此外，CKD 患者表现出血压和交感神经系统（SNS）过度升高体力活动期间的激活，这不仅会导致运动不耐受，而且还会与心血管死亡风险增加有关。这种夸张的神经循环运动期间的反应部分是由于 SNS 的反射激活增强肌肉传入神经的敏感性增强（即运动加压反射）；然而，导致 CKD 运动升压反射过度的机制仍不清楚。这拟议的项目将探索肌肉增强减少的潜在机制作用运动时间质 pH 值的变化，以及 CKD 中血压反应过度。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流动力学并增强 CKD 运动训练的益处。这些研究结果将为 CKD 特征的运动不耐受提供机制见解，并应用实用的药理学和行为疗法来解决这个高度相关的问题问题。