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

血压（BP）是维持器官灌注所必需的，也是心血管系统的一个关键调节变量。尽管这很重要，但健康个体在休息和运动后的血压存在很大差异。寻找导致这些个体间差异的机制是我研究项目的长期目标。我的实验室的初步数据发现了运动肌肉交感神经活动（MSNA）和BP反应的变异性的几种新机制。我们已经证明，在年轻男性中，肌肉中化学受体的遗传差异在调节运动血压方面发挥了重要作用，而在女性中则没有。我们现在将研究造成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（绝对力量）影响相对强度静态握力运动的BP反应，挑战当前的教条。我们提出的工作将确定这些发现是否适用于更大肌肉量的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，但我们发现运动时的MSNA反应与血压反应无关。相反，我们发现运动时的MSNA反应与血压负荷的相对变化有关。这表明动脉压力反射在这些反应中起重要作用。我们的研究结果发现，在两种不同类型的运动中，静态握力收缩和动态握力收缩，这种调节存在关键差异。我们现在必须调查造成这些差异的原因。一个悬而未决的问题是，为什么运动期间，MSNA的增加与血压反应的关系不大。对不同器官床（如心脏、肌肉、肾脏）的交感神经流出量可以有不同的控制，个体之间的交感神经总流出量可能相似，但对肌肉的相对流出量可能不同。我们将研究运动过程中交感神经向肌肉和肾脏流出的变化是否呈负相关。我们的初步发现提出了令人兴奋的新问题，突出了我们对运动时控制交感神经和BP反应的机制的不完整理解。本研究的短期目标是研究运动过程中遗传变异、绝对肌力、MSNA的动脉压力反射控制和交感神经外流的差异控制对血压反应的影响。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。所产生的新知识将大大促进我们对人类运动时控制交感神经和BP反应机制的基本理解。这将应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训练环境，重点是人类综合神经心血管生理学。

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.