Augmentation of endothelium-dependent vasodilatory signalling improves functional sympatholysis in contracting muscle of older adults.
Augmentation of endothelium-dependent vasodilatory signalling improves functional sympatholysis in contracting muscle of older adults.
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内皮依赖性血管舒张信号的增强可改善老年人收缩肌肉的功能性交感神经。
DOI：
10.1113/jp279462
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发表时间：
2020
期刊：
影响因子：
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通讯作者：
Dinenno,FrankA
中科院分区：
文献类型：
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作者：
HearonJr,ChristopherM;Richards,JenniferC;Racine,MathewL;Luckasen,GaryJ;Larson,DennisG;Dinenno,FrankA
要点收缩骨骼肌减弱交感血管收缩（功能性交感神经溶解）的能力对于运动介导的交感兴奋期间维持血流至关重要。功能性交感神经和内皮功能随着年龄的增长而受损，导致运动期间收缩骨骼肌的血流和氧气输送受损。在本研究中，动脉内输注ACh或ATP以增强运动过程中的内皮依赖性信号减弱了老年人收缩肌肉中的α1肾上腺素能血管收缩。能够进行功能性交感神经调节的血管信号传导机制在健康老龄化过程中得以保留，因此与年龄相关的功能性交感神经损伤可能是由于功能信号（例如血浆[ATP]）的丧失而不是内在的内皮功能障碍造成的。减弱的交感α-肾上腺素能血管收缩（“功能性交感神经松解”）随着年龄的增长而受损。在年轻人中，轻度运动期间内皮依赖性血管舒张信号的增加会增强交感神经的作用。在本研究中，我们测试了这样的假设：老年人运动期间增加内皮依赖性信号传导可以改善交感神经。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）并计算了在（i）单独输注内皮依赖性血管扩张剂（方案 1：ACh 或方案 2：低剂量 ATP）期间局部动脉内输注去氧肾上腺素（PE；α1 激动剂）时血管电导 (FVC) 的变化。 (ii) 轻度握力练习（5%最大自主收缩；MVC）； (iii) 适度的握力练习（15% MVC）； (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。在对照血管舒张剂输注期间，PE 引起静息骨骼肌的强烈血管收缩（ΔFVC：ACh：-31 ± 3 和 ATP：-30 ± 4%）。轻度或中度强度运动不会减弱 PE 介导的血管收缩（ΔFVC：5% MVC：-30 ± 9；15% MVC：-33 ± 8%；与对照 ACh 和 ATP 相比，P> 0.05），表明交感作用受损，轻度运动期间输注 ACh 或 ATP 不会影响这种反应。然而，在中等强度运动期间，通过输注 ACh 或 ATP 增强内皮依赖性信号传导，减弱了 PE 介导的血管收缩（ΔFVC：分别为 -13 ± 1 和 -19 ± 5%；与所有条件相比，P < 0.05）。我们的研究结果表明，如果给予足够的刺激，内皮依赖性交感神经在老年人中保持完整。旨在激活这些途径的策略代表了改善老年人交感神经作用、从而改善组织血流和氧气输送的可行方法。
Key pointsThe 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 α1‐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.AbstractThe 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; α1‐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> 0.05vs. 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< 0.05vs. 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.