TY - JOUR
T1 - Adenosine receptor-dependent signaling is not obligatory for normobaric and hypobaric hypoxia-induced cerebral vasodilation in humans
AU - Hoiland, Ryan L.
AU - Bain, Anthony R.
AU - Tymko, Michael M.
AU - Rieger, Mathew G.
AU - Howe, Connor A.
AU - Willie, Christopher K.
AU - Hansen, Alex B.
AU - Flück, Daniela
AU - Wildfong, Kevin W.
AU - Stembridge, Mike
AU - Subedi, Prajan
AU - Anholm, James
AU - Ainslie, Philip N.
PY - 2017/4/1
Y1 - 2017/4/1
N2 - 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 (PETO2) and carbon dioxide (PETCO2), 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% Sao2). Ventilation, PETO and PETCO2, 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 PETCO2 (P < 0.01). Upon mathematical correction for PETCO2, the CBF response to hypoxia was unaltered following theophylline. Cerebrovascular reactivity to hypoxia (i.e., response slope) was not different between trials, irrespective of PETCO2. 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.
AB - 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 (PETO2) and carbon dioxide (PETCO2), 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% Sao2). Ventilation, PETO and PETCO2, 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 PETCO2 (P < 0.01). Upon mathematical correction for PETCO2, the CBF response to hypoxia was unaltered following theophylline. Cerebrovascular reactivity to hypoxia (i.e., response slope) was not different between trials, irrespective of PETCO2. 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.
U2 - 10.1152/japplphysiol.00840.2016
DO - 10.1152/japplphysiol.00840.2016
M3 - Article
C2 - 28082335
AN - SCOPUS:85016967202
SN - 8750-7587
VL - 122
SP - 795
EP - 808
JO - Journal of Applied Physiology
JF - Journal of Applied Physiology
IS - 4
ER -