运动中和外源性 ATP 输注时衰老人体后突触 α-肾上腺素能血管收缩的调节。
Modulation of postjunctional α-adrenergic vasoconstriction during exercise and exogenous ATP infusions in ageing humans.
机构信息
Human Cardiovascular Physiology Laboratory, Department of Health and Exercise Science, Vascular Physiology Research Group, Colorado State University, Fort Collins, CO 80523-1582, USA.
出版信息
J Physiol. 2011 May 15;589(Pt 10):2641-53. doi: 10.1113/jphysiol.2010.204081. Epub 2011 Feb 28.
The ability to modulate sympathetic α-adrenergic vasoconstriction in contracting muscle is impaired with age. In young adults, adenosine triphosphate (ATP) has been shown to blunt sympathetic vasoconstrictor responsiveness similar to exercise. Therefore, we tested the hypothesis that modulation of postjunctional α-adrenergic vasoconstriction to exogenous ATP is impaired in ageing humans.We measured forearm blood flow (FBF; Doppler ultrasound) and calculated vascular conductance (FVC) to intra-arterial infusions of phenylephrine (α₁-agonist) and dexmedetomidine (α₂-agonist) during rhythmic handgrip exercise (15% MVC), a control non-exercise vasodilator condition (adenosine), and ATP infusion in seven older (64 ± 3 years) and seven young (22 ± 1 years) healthy adults. Forearm hyperaemia was matched across all vasodilatating conditions. During adenosine, forearm vasoconstrictor responses to direct α₁-stimulation were lower in older compared with young adults (ΔFVC=-25 ± 3% vs. -41 ± 5%; P <0.05), whereas the responses to α₂-stimulation were not different (-35±6% vs. -44 ± 8%; NS). During exercise, α₁-mediated vasoconstriction was significantly blunted compared with adenosine in both young (-9 ± 2% vs. -41 ± 5%) and older adults (-15 ± 2% vs. -25 ± 3%); however, the magnitude of sympatholysis was reduced in older adults (32 ± 13 vs. 74 ± 8%; P <0.05). Similarly, α₂-mediated vasoconstriction during exercise was significantly blunted in both young (-15 ± 4% vs. -44 ± 8%) and older adults (-26 ± 3% vs. -35 ± 6%), however the magnitude of sympatholysis was reduced in older adults (19 ± 8% vs. 60 ± 10%; P <0.05). During ATP, both α₁- and α₂-mediated vasoconstriction was nearly abolished in young and older adults (ΔFVC ∼ -5%), and the magnitude of sympatholysis was similar in both age groups (∼85-90%). Our findings indicate that the ability to modulate postjunctional α-adrenergic vasoconstriction during exercise is impaired with age, whereas the sympatholytic effect of exogenous ATP is preserved. Thus, if impairments in vascular control during exercise in older adults involve vasoactive ATP, we speculate that circulating ATP is reduced with advancing age.
在收缩的肌肉中调节交感α-肾上腺素能血管收缩的能力随着年龄的增长而下降。在年轻人中，已证明三磷酸腺苷 (ATP) 可类似运动一样使交感血管收缩反应迟钝。因此，我们测试了这样一个假设，即在衰老的人体中，对外源性 ATP 的节后 α-肾上腺素能血管收缩的调节作用受损。我们测量了前臂血流量（通过多普勒超声）并计算了血管传导率（FVC），以评估在节奏性握力运动（15%最大握力）、非运动性血管扩张剂条件（腺苷）和 ATP 输注期间，动脉内输注去氧肾上腺素（α₁-激动剂）和右美托咪定（α₂-激动剂）对内动脉的影响，在 7 名老年人（64±3 岁）和 7 名年轻人（22±1 岁）健康成年人中进行。在所有血管扩张条件下，前臂充血保持一致。在给予腺苷时，与年轻人相比，老年人直接刺激α₁时的前臂血管收缩反应较低（ΔFVC=-25±3% vs.-41±5%；P<0.05），而α₂刺激的反应没有差异（-35±6% vs.-44±8%；NS）。在运动过程中，与腺苷相比，年轻成年人（-9±2% vs.-41±5%）和老年人（-15±2% vs.-25±3%）的 α₁介导的血管收缩明显减弱；然而，老年人的交感神经抑制作用减弱（32±13% vs.74±8%；P<0.05）。同样，在年轻成年人（-15±4% vs.-44±8%）和老年人（-26±3% vs.-35±6%）中，运动时的 α₂介导的血管收缩也明显减弱，但老年人的交感神经抑制作用减弱（19±8% vs.60±10%；P<0.05）。在给予 ATP 时，年轻人和老年人的 α₁和 α₂介导的血管收缩几乎完全被抑制（ΔFVC≈-5%），并且在两组年龄中，交感神经抑制作用相似（≈85-90%）。我们的研究结果表明，在运动过程中调节节后 α-肾上腺素能血管收缩的能力随着年龄的增长而下降，而外源性 ATP 的交感神经抑制作用则得以保留。因此，如果老年人运动时血管控制的损害涉及血管活性 ATP，我们推测随着年龄的增长，循环 ATP 会减少。
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