Hearon Christopher M, Dinenno Frank A
Human Cardiovascular Physiology Laboratory, Department of Health and Exercise Science, Colorado State University, Fort Collins, CO, 80523, USA.
Center for Cardiovascular Research, Colorado State University, Fort Collins, CO, 80523, USA.
J Physiol. 2016 Apr 15;594(8):2261-73. doi: 10.1113/JP270593. Epub 2015 Nov 2.
The regulation of skeletal muscle blood flow and oxygen delivery to contracting skeletal muscle is complex and involves the mechanical effects of muscle contraction; local metabolic, red blood cell and endothelium-derived substances; and the sympathetic nervous system (SNS). With advancing age in humans, skeletal muscle blood flow is typically reduced during dynamic exercise and this is due to a lower vascular conductance, which could ultimately contribute to age-associated reductions in aerobic exercise capacity, a primary predictor of mortality in both healthy and diseased ageing populations. Recent findings have highlighted the contribution of endothelium-derived substances to blood flow control in contracting muscle of older adults. With advancing age, impaired nitric oxide availability due to scavenging by reactive oxygen species, in conjunction with elevated vasoconstrictor signalling via endothelin-1, reduces the local vasodilatory response to muscle contraction. Additionally, ageing impairs the ability of contracting skeletal muscle to blunt sympathetic vasoconstriction (i.e. 'functional sympatholysis'), which is critical for the proper regulation of tissue blood flow distribution and oxygen delivery, and could further reduce skeletal muscle perfusion during high intensity and/or large muscle mass exercise in older adults. We propose that initiation of endothelium-dependent hyperpolarization is the underlying signalling event necessary to properly modulate sympathetic vasoconstriction in contracting muscle, and that age-associated impairments in red blood cell adenosine triphosphate release and stimulation of endothelium-dependent vasodilatation may explain impairments in both local vasodilatation and functional sympatholysis with advancing age in humans.
骨骼肌血流调节以及向收缩的骨骼肌输送氧气的过程十分复杂，涉及肌肉收缩的机械效应、局部代谢、红细胞及内皮衍生物质，以及交感神经系统（SNS）。随着人类年龄的增长，动态运动期间骨骼肌血流量通常会减少，这是由于血管传导性降低所致，这最终可能导致与年龄相关的有氧运动能力下降，而有氧运动能力是健康和患病老年人群死亡率的主要预测指标。最近的研究结果突出了内皮衍生物质在老年人收缩肌肉的血流控制中的作用。随着年龄的增长，由于活性氧的清除作用导致一氧化氮可用性受损，同时内皮素-1介导的血管收缩信号增强，从而降低了对肌肉收缩的局部血管舒张反应。此外，衰老会损害收缩骨骼肌减弱交感神经血管收缩的能力（即“功能性交感神经抑制”），这对于组织血流分布和氧气输送的适当调节至关重要，并且可能进一步降低老年人在高强度和/或大肌肉量运动期间的骨骼肌灌注。我们认为，内皮依赖性超极化的启动是在收缩肌肉中适当调节交感神经血管收缩所必需的潜在信号事件，并且与年龄相关的红细胞三磷酸腺苷释放受损以及内皮依赖性血管舒张刺激可能解释了随着人类年龄增长局部血管舒张和功能性交感神经抑制的受损情况。
