Oxidative stress in severe pulmonary hypertension.
Severe pulmonary hypertension (PH) occurs in a primary or "unexplained" form and in a group of secondary forms associated with a number of diseases. Because the lung tissue from patients with severe PH demonstrates complex vascular lesions, which contain inflammatory cells, we wondered whether the lung tissue from patients with severe PH was "under oxidative stress." We used immunohistochemistry to localize nitrotyrosine and 8-hydroxy guanosine in the lung tissue sections from patients with primary and secondary PH. In some lung tissue extracts, the eicosanoid metabolites 5-oxo-eicosatetraenoic acid, leukotriene B4 5-hydroxyeicosatetraenoic acid (HETE), 12-HETE, and 15-HETE were measured using mass spectroscopy, and superoxide dismutase amount and activity were measured. Nitrotyrosine expression was ubiquitous in all PH lungs, and 5-oxo-eicosatetraenoic acid and HETE levels were elevated in the lungs of patients with severe PH but not in those lungs that were from the patients with severe PH treated chronically with prostacyclin. We conclude that indeed the lungs from patients with severe PH are under oxidative stress and that chronic prostacyclin infusion has an antiinflammatory effect on the lung tissue.
Bowers
Rebecca
R
Pulmonary Hypertension Center, University of Colorado Health Sciences Center, National Jewish Medical and Research Center, Denver 80262, USA.
Cool
Carlyne
C
Murphy
Robert C
RC
Tuder
Rubin M
RM
Hopken
Matthew W
MW
Flores
Sonia C
SC
Voelkel
Norbert F
NF
D001095:Arachidonic Acids / Q000378:metabolism; D006151:Guanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D006976:Hypertension, Pulmonary / Q000378:metabolism* / Q000473:pathology; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology*; D012720:Severity of Illness Index; D013482:Superoxide Dismutase / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
D001095:Arachidonic Acids; D006151:Guanosine; C080828:5-oxo-6,8,11,14-eicosatetraenoic acid; C002744:3-nitrotyrosine; C046215:8-hydroxyguanosine; D014443:Tyrosine; D013482:Superoxide Dismutase