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Adenosine receptor-dependent signaling is not obligatory for normobaric and hypobaric hypoxia-induced cerebral vasodilation in humans

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posted on 2022-11-28, 16:53 authored by Ryan L. Hoiland, Anthony R. Bain, Michael M. Tymko, Mathew G. Rieger, Connor A Howe, Christopher K. Willie, Alex B. Hansen, Daniela Flück, Kevin W. Wildfong, Michael StembridgeMichael Stembridge, Prajan Subedi, James Anholm, Philip N. Ainslie

 Hypoxia increases cerebral blood flow (CBF) with the underlying signaling processes potentially including adenosine. A randomized, double-blinded, and placebo-controlled design, was implemented to determine if adenosine receptor antagonism (theophylline, 3.75 mg/Kg) would reduce the CBF response to normobaric and hypobaric hypoxia. In 12 participants the partial pressures of end-tidal oxygen (PETO2PETO2) and carbon dioxide (PETCO2PETCO2), ventilation (pneumotachography), blood pressure (finger photoplethysmography), heart rate (electrocardiogram), CBF (duplex ultrasound), and intracranial blood velocities (transcranial Doppler ultrasound) were measured during 5-min stages of isocapnic hypoxia at sea level (98, 90, 80, and 70% SaO2SaO2). Ventilation, PETO2PETO2 and PETCO2PETCO2, blood pressure, heart rate, and CBF were also measured upon exposure (128 ± 31 min following arrival) to high altitude (3,800 m) and 6 h following theophylline administration. At sea level, although the CBF response to hypoxia was unaltered pre- and postplacebo, it was reduced following theophylline (P < 0.01), a finding explained by a lower PETCO2PETCO2 (P < 0.01). Upon mathematical correction for PETCO2PETCO2, the CBF response to hypoxia was unaltered following theophylline. Cerebrovascular reactivity to hypoxia (i.e., response slope) was not different between trials, irrespective of PETCO2PETCO2. At high altitude, theophylline (n = 6) had no effect on CBF compared with placebo (n = 6) when end-tidal gases were comparable (P > 0.05). We conclude that adenosine receptor-dependent signaling is not obligatory for cerebral hypoxic vasodilation in humans. 


Published in

Journal of Applied Physiology


American Physiological Society


  • AM (Accepted Manuscript)


Hoiland, R.L., Bain, A.R., Tymko, M.M., Rieger, M.G., Howe, C.A., Willie, C.K., Hansen, A.B., Flück, D., Wildfong, K.W., Stembridge, M. and Subedi, P. (2017) 'Adenosine receptor-dependent signaling is not obligatory for normobaric and hypobaric hypoxia-induced cerebral vasodilation in humans', Journal of Applied Physiology, 122(4), pp.795-808. DOI: 10.1152/japplphysiol.00840.2016

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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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