Mechanisms contributing to the inter-individual variability in neuro-cardiovascular responses to exercise

导致运动神经心血管反应个体间差异的机制

• 批准号: RGPIN-2020-04287
• 负责人: Millar, Philip
• 金额: $ 4.01万
• 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: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=757143
• 关键词: Mechanisms; contributing; inter; individual; variability

Blood pressure (BP) is essential to maintain organ perfusion and a key regulated variable of the cardiovascular system. Despite this importance, large variability in BP exists between healthy individuals at rest and in response to exercise. Finding the mechanisms responsible for these inter-individual differences is a long-term goal of my research program. Preliminary data from my laboratory has found several novel mechanisms for variability in exercise muscle sympathetic nerve activity (MSNA) and BP responses. We have shown important roles of genetic differences in chemical receptors in muscle for regulating exercise BP in young men but not women. We will now study the mechanism responsible for this sex difference and examine the influence of stretch sensitive muscle receptors. We have also shown that maximal muscle strength (absolute force) influences BP responses to relative intensity static handgrip exercise, challenging current dogma. Our proposed work will determine if these findings apply to larger muscle mass leg exercise or dynamic modes of contraction. The sympathetic nervous system is key for the regulation of BP, but we found that MSNA responses are unrelated to BP responses during exercise. Instead, we showed that the MSNA responses to exercise were related to the relative changes in BP loading. This suggests an important role of the arterial baroreflex in these responses. Our results found key differences in this regulation during two different types of exercise, static vs. dynamic handgrip contractions. We must now investigate what is the cause of these differences. A lingering question that remains is why increases in MSNA are poorly related to BP responses during exercise. Sympathetic outflow can be differentially controlled to distinct organ beds (e.g. heart, muscle, kidneys) and total sympathetic outflow may be similar between individuals but relative outflow to muscle could be different. We will study whether changes in sympathetic outflow to muscle and the kidneys are inversely related during exercise. Our preliminary findings have raised stimulating new questions that highlight our incomplete understanding of the mechanisms controlling sympathetic and BP responses to exercise. The short-term objectives of this proposal are to examine the influence of genetic variations, absolute muscle force, arterial baroreflex control of MSNA, and differential control of sympathetic outflow on BP responses during exercise. We will employ an integrative approach and conduct all proposed research in human participants. The new knowledge generated will significantly advance our fundamental understanding of the mechanisms controlling sympathetic and BP responses to exercise in humans. This will have applications for all cardiovascular fields. The proposed research program will also provide a high-quality and multi-faceted HQP training environment focused human integrative neuro-cardiovascular physiology.

血压（BP）对于维持器官灌注和心血管系统的关键调节变量至关重要。尽管这一点很重要，但在静止状态和对运动的响应中，健康个体之间存在巨大的BP差异。找到负责这些个体差异的机制是我的研究计划的长期目标。 我实验室的初步数据发现了运动肌肉交感神经活动（MSNA）和BP反应的几种新型机制。我们已经在化学受体中显示了肌肉中遗传差异的重要作用，以调节年轻男性而非女性的运动BP。现在，我们将研究导致这种性别差异的机制，并检查拉伸敏感肌肉受体的影响。我们还表明，最大肌肉强度（绝对力）会影响BP对相对强度静态手束运动的反应，这挑战了当前的教条。我们提出的工作将确定这些发现是否适用于较大的肌肉质量运动或动态收缩模式。 交感神经系统是BP调节的关键，但是我们发现MSNA反应与运动过程中的BP反应无关。取而代之的是，我们表明MSNA对运动的反应与BP负载的相对变化有关。这表明动脉压力反射在这些反应中的重要作用。我们的结果发现，在两种不同类型的练习中，静态和动态手绘收缩中的关键差异。现在，我们必须研究这些差异的原因是什么。剩下的一个挥之不去的问题是，为什么MSNA的增加与运动过程中的BP反应密不可分。交感神经流出可以差异地控制到不同的器官床（例如心脏，肌肉，肾脏），并且个人之间的交感神经流可能相似，但相对流出与肌肉的相对流出可能有所不同。我们将研究在运动过程中与肌肉和肾脏交感神经的变化是否成反比。我们的初步发现提出了刺激的新问题，这些问题突出了我们对控制同情和BP对运动的反应的机制的不完全理解。该提案的短期目标是检查遗传变异，绝对肌肉力量，动脉压力反射对MSNA的影响以及对交感神经流的差异控制对运动过程中BP反应的影响。我们将采用一种综合方法，并在人类参与者中进行所有拟议的研究。产生的新知识将大大提高我们对控制人类运动的同情和BP反应的机制的基本理解。这将为所有心血管田中提供应用。拟议的研究计划还将提供高质量和多方面的HQP培训环境，以人类综合神经性心血管生理学为重点。