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

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 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-cv(D)) 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-cv(D) 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.

• Authors: 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, Marc M Berger
• Journal: The Journal of physiology (J Physiol) Vol. 588 Issue Pt 23 Pg. 4837-47 (Dec 01 2010) ISSN: 1469-7793 [Electronic] England
• PMID: 20876202 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antihypertensive Agents
• Free Radicals
• Nitric Oxide
• Nifedipine
• Oxygen

Topics

• Adult
• Altitude Sickness (drug therapy, physiopathology)
• Antihypertensive Agents (therapeutic use)
• Female
• Free Radicals (chemistry, metabolism)
• Hemodynamics
• Humans
• Hypertension, Pulmonary (drug therapy, physiopathology)
• Lung (physiology)
• Male
• Middle Aged
• Molecular Structure
• Nifedipine (therapeutic use)
• Nitric Oxide (metabolism)
• Oxidative Stress (physiology)
• Oxygen (therapeutic use)
• Pulmonary Gas Exchange (physiology)