Romero Steven A, Ely Matthew R, Sieck Dylan C, Luttrell Meredith J, Buck Tahisha M, Kono Jordan M, Branscum Adam J, Halliwill John R
Department of Human Physiology, University of Oregon, Eugene, OR, 97403-1240, USA.
Exp Physiol. 2015 Apr 1;100(4):435-49. doi: 10.1113/EP085030. Epub 2015 Mar 25.
What is the central question of this study? Is exercise-induced oxidative stress the upstream exercise-related signalling mechanism that leads to sustained postexercise vasodilatation via activation of H1 and H2 histamine receptors? What is the main finding and its importance? Systemic administration of the antioxidant ascorbate inhibits sustained postexercise vasodilatation to the same extent as seen previously with H1 and H2 histamine receptor blockade following small muscle-mass exercise. However, ascorbate has a unique ability to catalyse the degradation of histamine. We also found that systemic infusion of the antioxidant N-acetylcysteine had no effect on sustained postexercise vasodilatation, suggesting that exercise-induced oxidative stress does not contribute to sustained postexercise vasodilatation. An acute bout of aerobic exercise elicits a sustained postexercise vasodilatation that is mediated by histamine H1 and H2 receptor activation. However, the upstream signalling pathway that leads to postexercise histamine receptor activation is unknown. We tested the hypothesis that the potent antioxidant ascorbate would inhibit this histaminergic vasodilatation following exercise. Subjects performed 1 h of unilateral dynamic knee extension at 60% of peak power in three conditions: (i) control; (ii) i.v. ascorbate infusion; and (iii) ascorbate infusion plus oral H1 /H2 histamine receptor blockade. Femoral artery blood flow was measured (using Doppler ultrasound) before exercise and for 2 h postexercise. Femoral vascular conductance was calculated as flow/pressure. Postexercise vascular conductance was greater for control conditions (3.4 ± 0.1 ml min(-1) mmHg(-1) ) compared with ascorbate (2.7 ± 0.1 ml min(-1) mmHg(-1) ; P < 0.05) and ascorbate plus H1 /H2 blockade (2.8 ± 0.1 ml min(-1) mmHg(-1) ; P < 0.05), which did not differ from one another (P = 0.9). Given that ascorbate may catalyse the degradation of histamine in vivo, we conducted a follow-up study, in which subjects performed exercise in two conditions: (i) control; and (ii) i.v. N-acetylcysteine infusion. Postexercise vascular conductance was similar for control (4.0 ± 0.1 ml min(-1) mmHg(-1) ) and N-acetylcysteine conditions (4.0 ± 0.1 ml min(-1) mmHg(-1) ; P = 0.8). Thus, the results in the initial study were due to the degradation of histamine in skeletal muscle by ascorbate, because the histaminergic vasodilatation was unaffected by N-acetylcysteine. Overall, exercise-induced oxidative stress does not appear to contribute to sustained postexercise vasodilatation.
本研究的核心问题是什么？运动诱导的氧化应激是否是通过激活H1和H2组胺受体导致运动后持续血管舒张的上游运动相关信号传导机制？主要发现及其重要性是什么？抗氧化剂抗坏血酸的全身给药抑制运动后持续血管舒张的程度与之前小肌肉量运动后H1和H2组胺受体阻断时所见相同。然而，抗坏血酸具有催化组胺降解的独特能力。我们还发现抗氧化剂N-乙酰半胱氨酸的全身输注对运动后持续血管舒张没有影响，这表明运动诱导的氧化应激对运动后持续血管舒张没有作用。一次急性有氧运动引发由组胺H1和H2受体激活介导的运动后持续血管舒张。然而，导致运动后组胺受体激活的上游信号通路尚不清楚。我们测试了强效抗氧化剂抗坏血酸会抑制运动后这种组胺能血管舒张的假设。受试者在三种情况下以峰值功率的60%进行1小时的单侧动态膝关节伸展：（i）对照；（ii）静脉输注抗坏血酸；（iii）抗坏血酸输注加口服H1/H2组胺受体阻断。在运动前和运动后2小时测量股动脉血流量（使用多普勒超声）。股血管传导率计算为流量/压力。对照条件下运动后血管传导率（3.4±0.1 ml·min⁻¹·mmHg⁻¹）高于抗坏血酸组（2.7±0.1 ml·min⁻¹·mmHg⁻¹；P<0.05）和抗坏血酸加H1/H2阻断组（2.8±0.1 ml·min⁻¹·mmHg⁻¹；P<0.05），而后两组之间无差异（P = 0.9）。鉴于抗坏血酸可能在体内催化组胺降解，我们进行了一项后续研究，其中受试者在两种情况下进行运动：（i）对照；（ii）静脉输注N-乙酰半胱氨酸。对照（4.0±0.1 ml·min⁻¹·mmHg⁻¹）和N-乙酰半胱氨酸条件下运动后血管传导率相似（4.0±0.1 ml·min⁻¹·mmHg⁻¹；P = 0.8）。因此，最初研究的结果是由于抗坏血酸使骨骼肌中的组胺降解，因为组胺能血管舒张不受N-乙酰半胱氨酸的影响。总体而言，运动诱导的氧化应激似乎对运动后持续血管舒张没有作用。
