title: Hypoxia increases exercise heart rate despite combined inhibition of β-adrenergic and muscarinic receptors.
abstract: 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 β-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 ± 1.2 l/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.
authors.affiliation: Center for Integrative Human Physiology, Institute of Physiology, University of Zürich, Zurich, Switzerland; Department of Environmental Physiology, School of Technology and Health, Royal Institute of Technology, Solna, Sweden; chrsie@kth.se.
authors.forename: C
authors.initials: C
authors.lastname: Siebenmann
authors.affiliation: Center for Integrative Human Physiology, Institute of Physiology, University of Zürich, Zurich, Switzerland; Department of Anesthesia, The Copenhagen Muscle Research Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark;
authors.forename: P
authors.initials: P
authors.lastname: Rasmussen
authors.affiliation: Department of Anesthesia, The Copenhagen Muscle Research Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark;
authors.forename: H
authors.initials: H
authors.lastname: Sørensen
authors.affiliation: Department of Nutrition, Exercise, and Sports, University of Copenhagen, Copenhagen, Denmark; and.
authors.forename: T C
authors.initials: TC
authors.lastname: Bonne
authors.affiliation: Department of Anesthesia, The Copenhagen Muscle Research Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark;
authors.forename: M
authors.initials: M
authors.lastname: Zaar
authors.affiliation: Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: N J
authors.initials: NJ
authors.lastname: Aachmann-Andersen
authors.affiliation: Department of Nutrition, Exercise, and Sports, University of Copenhagen, Copenhagen, Denmark; and.
authors.forename: N B
authors.initials: NB
authors.lastname: Nordsborg
authors.affiliation: Department of Anesthesia, The Copenhagen Muscle Research Centre, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark;
authors.forename: N H
authors.initials: NH
authors.lastname: Secher
authors.affiliation: Center for Integrative Human Physiology, Institute of Physiology, University of Zürich, Zurich, Switzerland;
authors.forename: C
authors.initials: C
authors.lastname: Lundby
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000328:Adult; D001642:Bicycling; D002302:Cardiac Output; D003718:Denmark; D015444:Exercise; D017079:Exercise Tolerance; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D000860:Hypoxia / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism; D012119:Respiration; D013610:Tachycardia / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D013997:Time Factors; D055815:Young Adult
chemical_list: D000319:Adrenergic beta-Antagonists; D018727:Muscarinic Antagonists; D011943:Receptors, Adrenergic, beta; D011976:Receptors, Muscarinic
keywords: altitude; antagonist; autonomic nervous system; parasympathetic; sympathetic