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High-altitude pulmonary hypertension is associated with a free radical-mediated reduction in pulmonary nitric oxide bioavailability

High altitude (HA)-induced pulmonary hypertension may be due to a free radical-mediated reduction in pulmonary nitric oxide (NO) bioavailability. We hypothesised that the increase in pulmonary artery systolic pressure (PASP) at HA would be associated with a net transpulmonary output of free radicals...

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Hauptverfasser: Bailey, Damian M. (VerfasserIn) , Dehnert, Christoph (VerfasserIn) , Luks, Andrew M. (VerfasserIn) , Menold, Elmar (VerfasserIn) , Castell, Christian (VerfasserIn) , Schendler, Guido (VerfasserIn) , Faoro, Vitalie (VerfasserIn) , Gutowski, Mariusz (VerfasserIn) , Evans, Kevin A. (VerfasserIn) , Taudorf, Sarah (VerfasserIn) , James, Philip E. (VerfasserIn) , McEneny, J. (VerfasserIn) , Young, Ian S. (VerfasserIn) , Swenson, Erik R. (VerfasserIn) , Mairbäurl, Heimo (VerfasserIn) , Bärtsch, Peter (VerfasserIn) , Berger, Marc Moritz (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 30 November 2010
In: The journal of physiology
Year: 2010, Jahrgang: 588, Heft: 23, Pages: 4837-4847
ISSN:1469-7793
DOI:10.1113/jphysiol.2010.194704
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1113/jphysiol.2010.194704
Verlag, lizenzpflichtig, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1113/jphysiol.2010.194704
Volltext
Verfasserangaben:Damian M. Bailey, Christoph Dehnert, Andrew M. Luks, Elmar Menold, Christian Castell, Guido Schendler, Vitalie Faoro, Mariusz Gutowski, Kevin A. Evans, Sarah Taudorf, Philip E. James, J. McEneny, Ian S. Young, Erik R. Swenson, Heimo Mairbäurl, Peter Bärtsch and Marc M. Berger
Beschreibung
Zusammenfassung:High altitude (HA)-induced pulmonary hypertension may be due to a free radical-mediated reduction in pulmonary nitric oxide (NO) bioavailability. We hypothesised that the increase in pulmonary artery systolic pressure (PASP) at HA would be associated with a net transpulmonary output of free radicals and corresponding loss of bioactive NO metabolites. Twenty-six mountaineers provided central venous and radial arterial samples at low altitude (LA) and following active ascent to 4559 m (HA). PASP was determined by Doppler echocardiography, pulmonary blood flow by inert gas re-breathing, and vasoactive exchange via the Fick principle. Acute mountain sickness (AMS) and high-altitude pulmonary oedema (HAPE) were diagnosed using clinical questionnaires and chest radiography. Electron paramagnetic resonance spectroscopy, ozone-based chemiluminescence and ELISA were employed for plasma detection of the ascorbate free radical (A·−), NO metabolites and 3-nitrotyrosine (3-NT). Fourteen subjects were diagnosed with AMS and three of four HAPE-susceptible subjects developed HAPE. Ascent decreased the arterio-central venous concentration difference (a-cvD) resulting in a net transpulmonary loss of ascorbate, α-tocopherol and bioactive NO metabolites (P < 0.05 vs. LA). This was accompanied by an increased a-cvD and net output of A·− and lipid hydroperoxides (P < 0.05 vs. sea level, SL) that correlated against the rise in PASP (r= 0.56-0.62, P < 0.05) and arterial 3-NT (r= 0.48-0.63, P < 0.05) that was more pronounced in HAPE. These findings suggest that increased PASP and vascular resistance observed at HA are associated with a free radical-mediated reduction in pulmonary NO bioavailability.
Beschreibung:Gesehen am 17.11.2022
Beschreibung:Online Resource
ISSN:1469-7793
DOI:10.1113/jphysiol.2010.194704

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