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Beta-adrenergic blockade increases pulmonary vascular resistance and causes exaggerated hypoxic pulmonary vasoconstriction at high altitude: a physiological study

Hilty, Matthias Peter; Siebenmann, Christoph; Rasmussen, Peter; Keiser, Stefanie; Müller, Andrea; Lundby, Carsten; Maggiorini, Marco (2024). Beta-adrenergic blockade increases pulmonary vascular resistance and causes exaggerated hypoxic pulmonary vasoconstriction at high altitude: a physiological study. European Heart Journal : Cardiovascular Pharmacotherapy, 10(4):316-328.

Abstract

BACKGROUND: An increasing number of hypertensive persons travel to high altitude while using antihypertensive medications such as betablockers. Nevertheless, while hypoxic exposure initiates an increase in pulmonary artery pressure (Ppa) and pulmonary vascular resistance (PVR), the contribution of the autonomic nervous system is unclear. In animals, $\beta$-adrenergic blockade has induced pulmonary vasoconstriction in normoxia and exaggerated hypoxic pulmonary vasoconstriction (HPV) and both effects were abolished by muscarinic blockade. We thus hypothesized that in humans propranolol (PROP) increases Ppa and PVR in normoxia and exaggerates HPV, and that these effects of PROP are abolished by glycopyrrolate (GLYC). METHODS: In seven healthy male lowlanders, pulmonary artery pressure was invasively measured without medication, with PROP and PROP+GLYC, both at sea level (SL, 488m) and after a three-week sojourn at 3454m altitude (HA). Bilateral thigh-cuff release maneuvers were performed to derive pulmonary pressure-flow relationships and pulmonary vessel distensibility. RESULTS: At SL, PROP increased Ppa and PVR from (mean±SEM) 14±1 to 17±1mmHg and from 69±8 to 108±11dyn*s*cm$^{−5}$ (21 and 57% increase, p=0.01 and p<0.0001). The PVR response to PROP was amplified at HA to 76% (p<0.0001, p[interaction]=0.05). At both altitudes, PROP+GLYC abolished the effect of PROP on Ppa and PVR. Pulmonary vessel distensibility decreased from 2.9±0.5 to 1.7±0.2 at HA (p<0.0001) and to 1.2±0.2 with PROP, and further decreased to 0.9±0.2%*mmHg$^{−1}$ with PROP+GLYC (p=0.01). CONCLUSIONS: Our data show that β-adrenergic blockade increases, and muscarinic blockade decreases PVR, whereas both increase pulmonary artery elastance. Future studies may confirm potential implications from the finding that β-adrenergic blockade exaggerates HPV for the management of mountaineers using β-blockers for prevention or treatment of cardiovascular conditions.

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Intensive Care Medicine
Dewey Decimal Classification:610 Medicine & health
Uncontrolled Keywords:Pharmacology (medical); Cardiology and Cardiovascular Medicine; acclimatization; autonomic nervous system; high altitude; hypoxia; pulmonary circulation; pulmonary hypertension
Language:English
Date:16 July 2024
Deposited On:16 Jan 2024 12:21
Last Modified:30 Oct 2024 02:40
Publisher:Oxford University Press
ISSN:2055-6837
Additional Information:This is a pre-copy-editing, author-produced PDF of an article accepted for publication in European Heart Journal : Cardiovascular Pharmacotherapy following peer review. The definitive publisher-authenticated version Matthias Peter Hilty, Christoph Siebenmann, Peter Rasmussen, Stefanie Keiser, Andrea Müller, Carsten Lundby, Marco Maggiorini, Beta-adrenergic blockade increases pulmonary vascular resistance and causes exaggerated hypoxic pulmonary vasoconstriction at high altitude: a physiological study is available online at: https://doi.org/10.1093/ehjcvp/pvae004.
OA Status:Closed
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1093/ehjcvp/pvae004
PubMed ID:38216517

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