Human Cardiovascular Physiology Laboratory, Department of Health and Exercise Science, Colorado State University, Fort Collins, CO, USA.
Medical Center of the Rockies Foundation, University of Colorado Health System, Loveland, CO, USA.
J Physiol. 2020 Jun;598(12):2323-2336. doi: 10.1113/JP279462. Epub 2020 May 14.
The ability of contracting skeletal muscle to attenuate sympathetic vasoconstriction (functional sympatholysis) is critical for maintaining blood flow during exercise-mediated sympathoexcitation. Functional sympatholysis and endothelial function are impaired with ageing, resulting in compromised blood flow and oxygen delivery to contracting skeletal muscle during exercise. In the present study, intra-arterial infusion of ACh or ATP to augment endothelium-dependent signalling during exercise attenuated α -adrenergic vasoconstriction in the contracting muscle of older adults. The vascular signalling mechanisms capable of functional sympatholysis are preserved in healthy ageing, and thus the age-related impairment in functional sympatholysis probably results from the loss of a functional signal (e.g. plasma [ATP]) as opposed to an intrinsic endothelial dysfunction.
The ability of contracting skeletal muscle to attenuate sympathetic α-adrenergic vasoconstriction ('functional sympatholysis') is impaired with age. In young adults, increasing endothelium-dependent vasodilatory signalling during mild exercise augments sympatholysis. In the present study, we tested the hypothesis that increasing endothelium-dependent signalling during exercise in older adults can improve sympatholysis. In 16 older individuals (Protocol 1, n = 8; Protocol 2, n = 8), we measured forearm blood flow (Doppler ultrasound) and calculated changes in vascular conductance (FVC) to local intra-arterial infusion of phenylephrine (PE; α -agonist) during (i) infusion of an endothelium-dependent vasodilator alone (Protocol 1: ACh or Protocol 2: low dose ATP); (ii) mild handgrip exercise (5% maximum voluntary contraction; MVC); (iii) moderate handgrip exercise (15% MVC); and (iv) mild or moderate handgrip exercise + infusion of ACh or ATP to augment endothelium-dependent signalling. PE caused robust vasoconstriction in resting skeletal muscle during control vasodilator infusions (ΔFVC: ACh: -31 ± 3 and ATP: -30 ± 4%). PE-mediated vasoconstriction was not attenuated by mild or moderate intensity exercise (ΔFVC: 5% MVC: -30 ± 9; 15% MVC: -33 ± 8%; P > 0.05 vs. control ACh and ATP), indicative of impaired sympatholysis, and ACh or ATP infusion during mild exercise did not impact this response. However, augmentation of endothelium-dependent signalling via infusion of ACh or ATP during moderate intensity exercise attenuated PE-mediated vasoconstriction (ΔFVC: -13 ± 1 and -19 ± 5%, respectively; P < 0.05 vs. all conditions). Our findings demonstrate that, given a sufficient stimulus, endothelium-dependent sympatholysis remains intact in older adults. Strategies aimed at activating such pathways represent a viable approach for improving sympatholysis and thus tissue blood flow and oxygen delivery in older adults.
收缩骨骼肌减弱交感神经血管收缩（功能性解交感作用）的能力对于在运动介导的交感兴奋期间维持血流至关重要。随着年龄的增长，功能性解交感作用和内皮功能受损，导致运动时收缩骨骼肌的血流和氧气输送受损。在本研究中，在运动期间，通过动脉内输注 ACh 或 ATP 来增强内皮依赖性信号传导，可减轻收缩肌肉中的 α-肾上腺素能血管收缩。在健康衰老中，能够进行功能性解交感作用的血管信号传导机制得以保留，因此，与年龄相关的功能性解交感作用受损可能是由于功能性信号（例如，血浆[ATP]）的丧失而不是内皮功能障碍的内在原因。
收缩骨骼肌减弱交感神经α-肾上腺素能血管收缩（“功能性解交感作用”）的能力会随着年龄的增长而下降。在年轻人中，在轻度运动期间增加内皮依赖性血管舒张信号可增强解交感作用。在本研究中，我们检验了以下假设：在老年人中，在运动期间增加内皮依赖性信号传导可以改善解交感作用。在 16 名老年人（方案 1，n=8；方案 2，n=8）中，我们测量了前臂血流量（多普勒超声），并计算了局部动脉内输注去氧肾上腺素（PE；α-激动剂）期间血管传导率（FVC）的变化（i）单独输注内皮依赖性血管扩张剂时（方案 1：ACh 或方案 2：低剂量 ATP）；（ii）轻度握力运动（5%最大自愿收缩；MVC）；（iii）中度握力运动（15%MVC）；和（iv）轻度或中度握力运动+输注 ACh 或 ATP 以增强内皮依赖性信号传导。在对照血管扩张剂输注期间，PE 引起静息骨骼肌中强烈的血管收缩（ΔFVC：ACh：-31±3 和 ATP：-30±4%）。轻度或中度强度运动并不能减轻 PE 介导的血管收缩（ΔFVC：5%MVC：-30±9；15%MVC：-33±8%；P>0.05 与对照 ACh 和 ATP），表明解交感作用受损，并且在轻度运动期间输注 ACh 或 ATP 并不影响这种反应。然而，在中度强度运动期间通过输注 ACh 或 ATP 增强内皮依赖性信号传导可减轻 PE 介导的血管收缩（ΔFVC：-13±1 和-19±5%，分别；P<0.05 与所有条件）。我们的发现表明，在老年人中，只要有足够的刺激，内皮依赖性解交感作用仍然完好。旨在激活这些途径的策略代表了改善解交感作用以及改善老年人组织血流和氧气输送的可行方法。
