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Adrenergic control of skeletal muscle blood flow during chronic hypoxia in healthy males

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posted on 2023-02-03, 14:53 authored by Lydia L. Simpson, Alexander B. Hansen, Gilbert Moralez, Sachin B. Amin, Florian Hofstaetter, Christopher Gasho, Michael StembridgeMichael Stembridge, Tony Dawkins, Michael M. Tymko, Philip N. Ainslie, Justin S. Lawley, Christopher M. Hearon Jr.

 Sympathetic transduction is reduced following chronic high-altitude (HA) exposure; however, vascular α-adrenergic signalling, 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 1) incremental intra-arterial infusion of phenylephrine to assess α1-adrenergic receptor responsiveness and 2) combined intra-arterial infusion of β-adrenergic and α-adrenergic antagonists propranolol and phentolamine (α-βblockade) to assess adrenergic vascular restraint at rest and during exercise-induced sympathoexcitation (cycling; 60% peak power). Experiments were performed near SL (344m) and following three-weeks at HA (4,380m). HA abolished the vasoconstrictor response to low-dose phenylephrine (ΔFVC: SL: -34±15%, vs HA; +3±18%; P<0.0001) and markedly attenuated the response to medium (ΔFVC: SL: -45±18% vs HA: -28±11%; P=0.009) and high (ΔFVC: SL: -47±20%, vs HA: -35±20%; P=0.041) doses. Blockade of β-adrenergic receptors alone had no effect on resting FVC (P=0.500) and combined α-βblockade induced a similar vasodilatory response at SL and HA (P=0.580). Forearm vasoconstriction during cycling was not different at SL and HA (P=0.999). Interestingly, cycling-induced forearm vasoconstriction was attenuated by α-βblockade at SL (ΔFVC: Control: -27±128 vs α-βblockade: +19±23%; P=0.0004), but unaffected at HA (ΔFVC: Control: -20±22 vs α-βblockade: -23±11%; P=0.999). Our results indicate that in healthy males, altitude acclimatization attenuates α1-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. 


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American Journal of Physiology-Regulatory, Integrative and Comparative Physiology


American Physiological Society


  • AM (Accepted Manuscript)


Simpson, L. L., Hansen, A. B., Moralez, G., Amin, S. B., Hofstaetter, F., Gasho, C., ... & Hearon Jr, C. M. (2023). Adrenergic control of skeletal muscle blood flow during chronic hypoxia in healthy males. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. doi: 10.1152/ajpregu.00230.2022

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Cardiff Met Affiliation

  • Cardiff School of Sport and Health Sciences

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Mike Stembridge

Cardiff Met Research Centre/Group

  • Cardiovascular Physiology

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