title: Parasympathetic withdrawal increases heart rate after 2 weeks at 3454 m altitude.
abstract: Heart rate is increased in chronic hypoxia and we tested whether this is the result of increased sympathetic nervous activity, reduced parasympathetic nervous activity, or a non-autonomic mechanism. In seven lowlanders, heart rate was measured at sea level and after 2 weeks at high altitude after individual and combined pharmacological inhibition of sympathetic and/or parasympathetic control of the heart. Inhibition of parasympathetic control of the heart alone or in combination with inhibition of sympathetic control abolished the high altitude-induced increase in heart rate. Inhibition of sympathetic control of the heart alone did not prevent the high altitude-induced increase in heart rate. These results indicate that a reduced parasympathetic nervous activity is the main mechanism underlying the elevated heart rate in chronic hypoxia.
  
  
  
  Chronic hypoxia increases resting heart rate (HR), but the underlying mechanism remains incompletely understood. We investigated the relative contributions of the sympathetic and parasympathetic nervous systems, along with potential non-autonomic mechanisms, by individual and combined pharmacological inhibition of muscarinic and/or β-adrenergic receptors. In seven healthy lowlanders, resting HR was determined at sea level (SL) and after 15-18 days of exposure to 3454 m high altitude (HA) without drug intervention (control, CONT) as well as after intravenous administration of either propranolol (PROP), or glycopyrrolate (GLYC), or PROP and GLYC in combination (PROP+GLYC). Circulating noradrenaline concentration increased from 0.9 ± 0.4 nmol l-1at SL to 2.7 ± 1.5 nmol l-1at HA (P = 0.03). The effect of HA on HR depended on the type of autonomic inhibition (P = 0.006). Specifically, HR was increased at HA from 64 ± 10 to 74 ± 12 beats min-1during the CONT treatment (P = 0.007) and from 52 ± 4 to 59 ± 5 beats min-1during the PROP treatment (P < 0.001). In contrast, HR was similar between SL and HA during the GLYC treatment (110 ± 7 and 112 ± 5 beats min-1, P = 0.28) and PROP+GLYC treatment (83 ± 5 and 85 ± 5 beats min-1, P = 0.25). Our results identify a reduction in cardiac parasympathetic activity as the primary mechanism underlying the elevated HR associated with 2 weeks of exposure to hypoxia. Unexpectedly, the sympathoactivation at HA that was evidenced by increased circulating noradrenaline concentration had little effect on HR, potentially reflecting down-regulation of cardiac β-adrenergic receptor function in chronic hypoxia. These effects of chronic hypoxia on autonomic control of the heart may concern not only HA dwellers, but also patients with disorders that are associated with hypoxaemia.
authors.affiliation: Centre for Integrative Human Physiology, Institute of Physiology, University of Zürich, Zürich, Switzerland.|Department of Environmental Physiology, School of Technology and Health, Royal Institute of Technology, Solna, Sweden.
authors.forename: Christoph
authors.identifier: 0000-0002-0315-3761
authors.initials: C
authors.lastname: Siebenmann
authors.affiliation: Centre for Integrative Human Physiology, Institute of Physiology, University of Zürich, Zürich, Switzerland.|H. Lundbeck A/S, Valby, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Rasmussen
authors.affiliation: Centre for Integrative Human Physiology, Institute of Physiology, University of Zürich, Zürich, Switzerland.
authors.forename: Mike
authors.initials: M
authors.lastname: Hug
authors.affiliation: Centre for Integrative Human Physiology, Institute of Physiology, University of Zürich, Zürich, Switzerland.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Keiser
authors.affiliation: Centre for Integrative Human Physiology, Institute of Physiology, University of Zürich, Zürich, Switzerland.
authors.forename: Daniela
authors.initials: D
authors.lastname: Flück
authors.affiliation: School of Sport, Exercise and Rehabilitation Sciences, College of Life and Environmental Sciences, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
authors.forename: James P
authors.initials: JP
authors.lastname: Fisher
authors.affiliation: Intensive Care Unit, University Hospital of Zürich, Zürich, Switzerland.
authors.forename: Matthias P
authors.identifier: 0000-0002-2765-881X
authors.initials: MP
authors.lastname: Hilty
authors.affiliation: Intensive Care Unit, University Hospital of Zürich, Zürich, Switzerland.
authors.forename: Marco
authors.initials: M
authors.lastname: Maggiorini
authors.affiliation: Centre for Integrative Human Physiology, Institute of Physiology, University of Zürich, Zürich, Switzerland.
authors.forename: Carsten
authors.initials: C
authors.lastname: Lundby
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000328:Adult; D000531:Altitude; D006024:Glycopyrrolate / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D000860:Hypoxia / Q000097:blood / Q000503:physiopathology; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009638:Norepinephrine / Q000097:blood; D010275:Parasympathetic Nervous System / Q000502:physiology*; D011433:Propranolol / Q000494:pharmacology; D055815:Young Adult
chemical_list: D000319:Adrenergic beta-Antagonists; D018727:Muscarinic Antagonists; D011433:Propranolol; D006024:Glycopyrrolate; D009638:Norepinephrine
keywords: autonomic nervous system; hypoxia; sympathetic