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)是维持器官血流灌注所必需的，也是心血管系统的关键调节变量。尽管这一点很重要，但健康的人在休息时和运动后的血压存在很大的差异。找到造成这些个体间差异的机制是我研究计划的长期目标。 来自我的实验室的初步数据发现了运动中肌肉交感神经活动(MSNA)和BP反应的几种新的变异性机制。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运动血压方面的重要作用，而不是女性。我们现在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，最大肌肉力量(绝对力)会影响BP对相对强度的静态握手练习的反应，这对目前的教条提出了挑战。我们提议的工作将确定这些发现是否适用于更大的肌肉质量、腿部运动或动态收缩模式。 交感神经系统是调节血压的关键，但我们发现MSNA反应与运动中的血压反应无关。相反，我们发现MSNA对运动的反应与BP负荷的相对变化有关。这表明动脉压力感受性反射在这些反应中起着重要作用。我们的结果发现，在两种不同类型的运动中，静态握力收缩和动态握力收缩时，这一调节机制存在关键差异。我们现在必须调查这些差异的原因是什么。一个挥之不去的问题是，为什么运动中MSNA的增加与BP的反应关系不大。交感神经流出可以不同地控制到不同的器官床(例如心脏、肌肉、肾脏)，交感神经总流出在个体之间可能是相似的，但相对肌肉流出可能是不同的。我们将研究在运动过程中，交感神经流出到肌肉和肾脏的变化是否呈负相关。 我们的初步发现提出了激动人心的新问题，突显了我们对控制交感神经和BP对运动反应的机制的不完全理解。这项建议的短期目标是检查遗传变异、绝对肌肉力量、MSNA的动脉压力感受性反射控制以及交感神经流出的不同控制对运动中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。产生的新知识将极大地促进我们对人类对运动的交感神经和血压反应的控制机制的基本理解。这将适用于所有心血管领域。拟议的研究计划还将提供高质量和多方面的HQP培训环境，专注于人类综合神经-心血管生理学。