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: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=716921
• 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）是维持器官灌注和心血管系统的关键调节变量所必需的。尽管如此重要，健康个体在休息和运动时的血压存在很大的差异。找到这些个体间差异的机制是我研究计划的长期目标。 从我的实验室的初步数据已经发现了运动肌肉交感神经活动（MSNA）和BP反应的变化的几个新的机制。我们已经证明了肌肉中化学受体的遗传差异在调节年轻男性而不是女性运动血压中的重要作用。我们现在将研究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，最大的肌肉力量（绝对力）影响相对强度的静态握力运动的BP反应，挑战目前的教条。我们提出的工作将确定这些发现是否适用于更大的肌肉质量腿部锻炼或动态收缩模式。 交感神经系统是血压调节的关键，但我们发现MSNA反应与运动期间的血压反应无关。相反，我们发现运动引起的MSNA反应与BP负荷的相对变化有关。这表明动脉压力感受器反射在这些反应中的重要作用。我们的研究结果发现，在两种不同类型的运动，静态与动态握收缩，这种调节的关键差异。我们现在必须研究这些差异的原因是什么。一个挥之不去的问题是，为什么MSNA的增加与运动期间的BP反应关系不大。交感神经流出可以被不同地控制到不同的器官床（例如心脏、肌肉、肾脏），并且总交感神经流出在个体之间可以是相似的，但是到肌肉的相对流出可以是不同的。我们将研究运动过程中交感神经流出到肌肉和肾脏的变化是否呈负相关。 我们的初步研究结果提出了刺激的新问题，突出了我们的不完全理解的机制控制交感神经和BP运动的反应。这项建议的短期目标是研究遗传变异，绝对肌肉力量，动脉压力感受器反射控制MSNA，和交感神经流出的差分控制在运动过程中对BP反应的影响。我们将采用综合方法，并在人类参与者中进行所有拟议的研究。产生的新知识将显着推进我们对人类运动控制交感神经和BP反应机制的基本理解。这将适用于所有心血管领域。拟议的研究计划还将提供一个高质量和多方面的HQP培训环境，重点是人类综合神经-心血管生理学。