TY - JOUR
T1 - Hypoxia increases exercise heart rate despite combined inhibition of β-adrenergic and muscarinic receptors
AU - Siebenmann, Christoph
AU - Rasmussen, Peter
AU - Sørensen, Henrik
AU - Bonne, Thomas Christian
AU - Zaar, Morten
AU - Aachmann-Andersen, Niels Jacob
AU - Nordsborg, Nikolai Baastrup
AU - Secher, Niels H.
AU - Lundby, Carsten
N1 - CURIS 2015 NEXS 223
PY - 2015/6/15
Y1 - 2015/6/15
N2 - Hypoxia increases the heart rate response to exercise, but the mechanism(s) remains unclear. We tested the hypothesis that the tachycardic effect of hypoxia persists during separate, but not combined, inhibition of (3-adrenergic and muscarinic receptors. Nine subjects performed incremental exercise to exhaustion in normoxia and hypoxia (fraction of inspired O2 = 12%) after intravenous administration of 1) no drugs (Cont), 2) propranolol (Prop), 3) glycopyrrolate (Glyc), or 4) Prop + Glyc. HR increased with exercise in all drug conditions (P < 0.001) but was always higher at a given workload in hypoxia than normoxia (P < 0.001). Averaged over all workloads, the difference between hypoxia and normoxia was 19.8 ± 13.8 beats/min during Cont and similar (17.2 ± 7.7 beats/min, P = 0.95) during Prop but smaller (P < 0.001) during Glyc and Prop + Glyc (9.8 ± 9.6 and 8.1 ± 7.6 beats/min, respectively). Cardiac output was enhanced by hypoxia (P < 0.002) to an extent that was similar between Cont, Glyc, and Prop + Glyc (2.3 ± 1.9, 1.7 ± 1.8, and 2.3 ± 1.2l/min, respectively, P> 0.4) but larger during Prop (3.4 ± 1.6 l/min, P = 0.004). Our results demonstrate that the tachycardic effect of hypoxia during exercise partially relies on vagal withdrawal. Conversely, sympathoexcitation either does not contribute or increases heart rate through mechanisms other than β-adrenergic transmission. A potential candidate is α-adrenergic transmission, which could also explain why a tachycardic effect of hypoxia persists during combined β-adrenergic and muscarinic receptor inhibition.
AB - Hypoxia increases the heart rate response to exercise, but the mechanism(s) remains unclear. We tested the hypothesis that the tachycardic effect of hypoxia persists during separate, but not combined, inhibition of (3-adrenergic and muscarinic receptors. Nine subjects performed incremental exercise to exhaustion in normoxia and hypoxia (fraction of inspired O2 = 12%) after intravenous administration of 1) no drugs (Cont), 2) propranolol (Prop), 3) glycopyrrolate (Glyc), or 4) Prop + Glyc. HR increased with exercise in all drug conditions (P < 0.001) but was always higher at a given workload in hypoxia than normoxia (P < 0.001). Averaged over all workloads, the difference between hypoxia and normoxia was 19.8 ± 13.8 beats/min during Cont and similar (17.2 ± 7.7 beats/min, P = 0.95) during Prop but smaller (P < 0.001) during Glyc and Prop + Glyc (9.8 ± 9.6 and 8.1 ± 7.6 beats/min, respectively). Cardiac output was enhanced by hypoxia (P < 0.002) to an extent that was similar between Cont, Glyc, and Prop + Glyc (2.3 ± 1.9, 1.7 ± 1.8, and 2.3 ± 1.2l/min, respectively, P> 0.4) but larger during Prop (3.4 ± 1.6 l/min, P = 0.004). Our results demonstrate that the tachycardic effect of hypoxia during exercise partially relies on vagal withdrawal. Conversely, sympathoexcitation either does not contribute or increases heart rate through mechanisms other than β-adrenergic transmission. A potential candidate is α-adrenergic transmission, which could also explain why a tachycardic effect of hypoxia persists during combined β-adrenergic and muscarinic receptor inhibition.
U2 - 10.1152/ajpheart.00861.2014
DO - 10.1152/ajpheart.00861.2014
M3 - Journal article
C2 - 25888515
SN - 0363-6135
VL - 308
SP - H1540-H1546
JO - American Journal of Physiology: Heart and Circulatory Physiology
JF - American Journal of Physiology: Heart and Circulatory Physiology
IS - 12
ER -