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 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.
Bailey
Damian M
DM
Neurovascular Research Laboratory, Faculty of Health, Science and Sport, University of Glamorgan, South Wales, UK. dbailey1@glam.ac.uk
Dehnert
Christoph
C
Luks
Andrew M
AM
Menold
Elmar
E
Castell
Christian
C
Schendler
Guido
G
Faoro
Vitalie
V
Gutowski
Mariusz
M
Evans
Kevin A
KA
Taudorf
Sarah
S
James
Philip E
PE
McEneny
J
J
Young
Ian S
IS
Swenson
Erik R
ER
Mairbäurl
Heimo
H
Bärtsch
Peter
P
Berger
Marc M
MM
D000328:Adult; D000532:Altitude Sickness / Q000188:drug therapy / Q000503:physiopathology; D000959:Antihypertensive Agents / Q000627:therapeutic use; D005260:Female; D005609:Free Radicals / Q000737:chemistry / Q000378:metabolism*; D006439:Hemodynamics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000503:physiopathology; D008168:Lung / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D015394:Molecular Structure; D009543:Nifedipine / Q000627:therapeutic use; D009569:Nitric Oxide / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D010100:Oxygen / Q000627:therapeutic use; D011659:Pulmonary Gas Exchange / Q000502:physiology
D000959:Antihypertensive Agents; D005609:Free Radicals; D009569:Nitric Oxide; D009543:Nifedipine; D010100:Oxygen