Bailey, Damian M., Dehnert, Christoph, Luks, Andrew M., Menold, Elmar, Castell, Christian, Schendler, Guido, Faoro, Vitalie, Gutowski, Mariusz, Evans, Kevin A., Taudorf, Sarah, James, Philip Eurig, McEneny, J., Young, Ian S., Swenson, Erik R., Mairbäurl, Heimo, Bärtsch, Peter and Berger, Marc M. 2010. High-altitude pulmonary hypertension is associated with a free radical-mediated reduction in pulmonary nitric oxide bioavailability. The Journal of Physiology 588 (23) , pp. 4837-4847. 10.1113/jphysiol.2010.194704 |
Abstract
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 mountaineersprovided central venous andradial arterial samples at lowaltitude (LA) and following active ascent to 4559m(HA).PASPwas determined byDoppler 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.Electronparamagnetic 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 bioactiveNOmetabolites (P <0.05 vs. LA). This was accompanied by an increased a-cvD and net output ofA•− 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.
Item Type: | Article |
---|---|
Date Type: | Publication |
Status: | Published |
Schools: | Medicine |
Subjects: | Q Science > QP Physiology R Medicine > R Medicine (General) |
Publisher: | The Physiological Society |
ISSN: | 0022-3751 |
Last Modified: | 19 Mar 2016 22:49 |
URI: | https://orca.cardiff.ac.uk/id/eprint/28388 |
Citation Data
Cited 80 times in Scopus. View in Scopus. Powered By Scopus® Data
Actions (repository staff only)
Edit Item |