Department of Sport Science, Division of Performance Physiology and Prevention, Universität Innsbruck, Innsbruck, Austria.
Department of Applied Clinical Research, University of Texas Southwestern Medical Center, Dallas, Texas, United States.
Am J Physiol Regul Integr Comp Physiol. 2023 Apr 1;324(4):R457-R469. doi: 10.1152/ajpregu.00230.2022. Epub 2023 Jan 30.
Sympathetic transduction is reduced following chronic high-altitude (HA) exposure; however, vascular α-adrenergic signaling, the primary mechanism mediating sympathetic vasoconstriction at sea level (SL), has not been examined at HA. In nine male lowlanders, we measured forearm blood flow (Doppler ultrasound) and calculated changes in vascular conductance (ΔFVC) during ) incremental intra-arterial infusion of phenylephrine to assess α-adrenergic receptor responsiveness and ) combined intra-arterial infusion of β-adrenergic and α-adrenergic antagonists propranolol and phentolamine (α-β-blockade) to assess adrenergic vascular restraint at rest and during exercise-induced sympathoexcitation (cycling; 60% peak power). Experiments were performed near SL (344 m) and after 3 wk at HA (4,383 m). HA abolished the vasoconstrictor response to low-dose phenylephrine (ΔFVC: SL: -34 ± 15%, vs. HA; 3 ± 18%; < 0.0001) and markedly attenuated the response to medium (ΔFVC: SL: -45 ± 18% vs. HA: -28 ± 11%; = 0.009) and high (ΔFVC: SL: -47 ± 20%, vs. HA: -35 ± 20%; = 0.041) doses. Blockade of β-adrenergic receptors alone had no effect on resting FVC ( = 0.500) and combined α-β-blockade induced a similar vasodilatory response at SL and HA ( = 0.580). Forearm vasoconstriction during cycling was not different at SL and HA ( = 0.999). Interestingly, cycling-induced forearm vasoconstriction was attenuated by α-β-blockade at SL (ΔFVC: Control: -27 ± 128 vs. α-β-blockade: +19 ± 23%; = 0.0004), but unaffected at HA (ΔFVC: Control: -20 ± 22 vs. α-β-blockade: -23 ± 11%; = 0.999). Our results indicate that in healthy males, altitude acclimatization attenuates α-adrenergic receptor responsiveness; however, resting α-adrenergic restraint remains intact, due to concurrent resting sympathoexcitation. Furthermore, forearm vasoconstrictor responses to cycling are preserved, although the contribution of adrenergic receptors is diminished, indicating a reliance on alternative vasoconstrictor mechanisms.
交感神经传递在慢性高海拔（HA）暴露后减少；然而，血管α-肾上腺素能信号，在海平面（SL）介导交感神经血管收缩的主要机制，尚未在 HA 进行检查。在九名男性低地人中，我们测量了前臂血流（多普勒超声），并计算了在递增动脉内输注苯肾上腺素期间血管传导的变化（ΔFVC），以评估α-肾上腺素能受体反应性和）同时进行动脉内输注β-肾上腺素能和α-肾上腺素能拮抗剂普萘洛尔和酚妥拉明（α-β 阻断）以评估在休息和运动引起的交感神经兴奋（循环；60%峰值功率）期间的肾上腺素能血管约束。实验在接近 SL（344 m）和海拔 3 周后在 HA（4,383 m）进行。HA 消除了低剂量苯肾上腺素引起的血管收缩反应（ΔFVC：SL：-34 ± 15%，vs. HA；3 ± 18%；< 0.0001），并显著减弱了中剂量（ΔFVC：SL：-45 ± 18% vs. HA：-28 ± 11%；= 0.009）和高剂量（ΔFVC：SL：-47 ± 20%，vs. HA：-35 ± 20%；= 0.041）的反应。单独阻断β-肾上腺素能受体对休息时的 FVC 没有影响（= 0.500），并且在 SL 和 HA 时联合α-β 阻断诱导了类似的血管扩张反应（= 0.580）。在 SL 和 HA 时，循环过程中的前臂血管收缩没有差异（= 0.999）。有趣的是，在 SL 时，α-β 阻断会减弱循环诱导的前臂血管收缩（ΔFVC：Control：-27 ± 128 vs. α-β-blockade：+19 ± 23%；= 0.0004），但在 HA 时不受影响（ΔFVC：Control：-20 ± 22 vs. α-β-blockade：-23 ± 11%；= 0.999）。我们的结果表明，在健康男性中，海拔适应会减弱α-肾上腺素能受体的反应性；然而，由于静息时交感神经兴奋，静息时的α-肾上腺素能约束仍然完整。此外，尽管肾上腺素能受体的贡献减少，但循环引起的前臂血管收缩反应得到保留，这表明依赖于替代的血管收缩机制。
