Evidence for differential control of muscle sympathetic fibres in humans

人类肌肉交感纤维差异控制的证据

• 批准号: RGPIN-2015-06019
• 负责人: Millar, Philip
• 金额: $ 2.04万
• 依托单位: University of Guelph
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=659793
• 关键词: Evidence; differential; control; muscle; sympathetic

The long-term goal of my research program is to advance our understanding of the mechanisms that control sympathetic nervous system (SNS) outflow and the circulation in humans. Activation of the SNS leads to increased heart rate, retention of water and sodium, and vasoconstriction of blood vessels. These actions make the SNS important for controlling blood pressure, a necessity to drive blood flow and deliver nutrients throughout the body. To understand the mechanisms responsible for maintaining circulatory homeostasis we need to know how sympathetic outflow is regulated. Our view of the SNS has been shaped by the methods available to measure outflow.  Initially, we thought that sympathetic outflow occurred in a general systemic fashion throughout the whole body. This concept was overturned with the discovery that measurements of regional sympathetic activity could be different to individuals organs (e.g. to the heart, kidneys, muscle). Using a state-of-the-art method, my recent work, the first in humans, suggests that in older or diseased subjects regulation of sympathetic outflow can extend to the control of individual sympathetic fibres (or single-units) within a nerve. This means that individual fibres can be increased or decreased separately, providing greater sensitivity in optimizing the sympathetic response to a perturbation. We will now use this technically demanding method, not available in many laboratories in Canada, to measure the behaviour of individual sympathetic fibres in order to establish conclusively that sympathetic outflow is regulated at the individual fibre level.  To answer this question, we need to demonstrate consistently that individual fibres can be differentially regulated in normal young subjects and in response to a variety of afferent stimuli. The short-term objectives of the proposal are to address these knowledge gaps. We have three main aims to address in this short-term research proposal, with each investigating the concepts of differential control and the regulation of muscle sympathetic single-units. We will conduct studies designed to test whether muscle sympathetic single-units can be individually regulated (evidenced by two single-unit sub-populations with opposite discharge characteristics) in response to selective afferent stimulation or an integrated exercise challenge (leg cycling); the functional impact of single-unit firing pattern on blood flow; and the mechanisms responsible for controlling the firing of sympathetic single-units. The novel results of these studies will provide fundamental information on the organization and regulation of the SNS in humans. This will have broad applications for identifying the mechanisms responsible for the homeostatic control of blood pressure at rest and during perturbations, such as exercise.

我的研究计划的长期目标是促进我们对控制交感神经系统（SNS）出口和人类流通的机制的理解。 SNS的激活导致心率增加，水和钠的保留以及血管血管的血管收缩。这些动作使SNS对于控制血压很重要，这是驱动血液流动并在整个身体中提供营养的必要条件。要了解负责维持循环系统稳态的机制，我们需要知道如何调节交感神经产出。我们对SNS的看法是通过可用于测量输出的方法来塑造的。最初，我们认为同情输出以整个身体的一般全身方式发生。这一概念被发现的发现是，区域交感活动的测量可能与个体器官不同（例如心脏，肾脏，肌肉）。使用最先进的方法，我最近的工作，即人类的第一项，表明，在较老的或犹豫不决的受试者中，交感神经流出可以扩展到神经系统中单个交感神经纤维（或单个单独）的控制。这意味着可以单独增加或分别减少单个纤维，从而在优化对扰动的同情反应方面具有更大的敏感性。现在，我们将使用这种技术要求的方法，在加拿大的许多实验室中不可用，以衡量单个交感神经纤维的行为，以便确定在单个纤维水平上调节交感神经出口。为了回答这个问题，我们需要始终证明，在正常的年轻受试者中可以对单个纤维进行不同的调节，并响应各种传入刺激。该提案的短期目标是解决这些知识差距。在这项短期研究建议中，我们有三个主要的目的可以解决，每个研究都调查了差异控制的概念和肌肉交感神经单间的调节。我们将进行旨在测试是否可以单独调节肌肉交感神经单间的研究（由两个具有相反放电特征的单单元子选集证明），以响应选择性传入刺激或综合运动挑战（腿部循环）；单单元发射模式对血流的功能影响；以及负责控制交感神经单位发射的机制。这些研究的新结果将提供有关人类中SNS的组织和调节的基本信息。这将有广泛的应用，以识别负责在休息和扰动期间（例如运动）对血压的稳态控制的机制。