Interstitial Norepinephrine and Exercise

间质去甲肾上腺素和运动

• 批准号: 7033866
• 负责人: Lawrence I Sinoway
• 金额: $ 30.06万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7033866
• 关键词: adenosine triphosphate; clinical research; exercise; high performance liquid chromatography; human subject; interstitial; microdialysis; muscle contraction; neurotransmitter transport; nitric oxide; norepinephrine; physiology; potassium; smooth muscle; striated muscles; vasoconstriction

DESCRIPTION (provided by applicant): The long-range goal of the principal investigator is to examine the mechanisms that regulate the autonomic nervous system. The specific goals of this program are to better understand the mechanisms regulating interstitial NE concentrations ((NE)i during exercise in humans. NE release evokes smooth muscle contractions and vasoconstriction. Our first aim in this proposal is to examine in human subjects the effects of changes in the interstitial concentration of potassium, nitric oxide and ATP on (NE)i. We hypothesize that potassium, NO and ATP will raise (NE)i. We will then explore the mechanisms by which these substances mediate their postulated effects. Our second aim is to examine and compare (NE)i in contracting and resting muscle during one-legged exercise. We hypothesize the (NE)i will be greater in contracting than in non-contracting muscle. We will then attempt to locally and selectively modify the interstitial milieu in order to better understand the determinants of (NE)i during exercise. Preliminary data from our laboratory suggests that the (NE)i in skeletal muscle is approximately 5.5 times the plasma concentration and is likely to be far more reflective of events within the neurovascular junction than plasma NE determinations or measurements of NE spillover (determined with radiotracer methods). A key feature of this proposal is that we will use microdialysis techniques in human subjects to determine (NE)i. To the best of our knowledge, experiments such as these have never been performed in human subjects. The work will be performed in a NIH funded General Clinical Research Center (GCRC) housed in the College of Medicine at the Hershey Medical Center, Hershey, PA.

描述（由申请人提供）：委托人的长期目标 研究者的任务是检查调节自主神经的机制 系统。该计划的具体目标是更好地了解 运动期间调节间质 NE 浓度 ((NE)i 的机制 人类。 NE 释放引起平滑肌收缩和血管收缩。我们的 该提案的首要目标是检查人类受试者的影响 钾、一氧化氮和 ATP 间质浓度的变化 (NE)i。我们假设钾、NO 和 ATP 会升高 (NE)i。我们随后将 探索这些物质介导其假设的机制 影响。我们的第二个目标是检查和比较 (NE)i 在承包和 单腿运动期间肌肉的休息。我们假设 (NE)i 将是 收缩的肌肉比非收缩的肌肉更大。然后我们将尝试 局部地、选择性地修改间隙环境，以便更好地 了解运动期间 (NE)i 的决定因素。我们的初步数据 实验室表明骨骼肌中的 (NE)i 约为 5.5 倍于血浆浓度，并且可能更能反映 神经血管接头内的事件比血浆 NE 测定或 NE 溢出的测量（用放射性示踪剂方法测定）。一把钥匙 该提案的特点是我们将在人体中使用微透析技术 确定 (NE)i 的受试者。据我们所知，实验如 这些从未在人类受试者中进行过。该工作将被执行 位于学院内的 NIH 资助的普通临床研究中心 (GCRC) 宾夕法尼亚州好时好时医疗中心医学博士。