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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. 

History

Published in

American Journal of Physiology-Regulatory, Integrative and Comparative Physiology

Publisher

American Physiological Society

Version

  • AM (Accepted Manuscript)

Citation

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

Print ISSN

0363-6119

Electronic ISSN

1522-1490

Cardiff Met Affiliation

  • Cardiff School of Sport and Health Sciences

Cardiff Met Authors

Mike Stembridge

Cardiff Met Research Centre/Group

  • Cardiovascular Physiology

Copyright Holder

  • © The Publisher

Language

  • en

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