Biochemical reaction products of nitric oxide as quantitative markers of primary pulmonary hypertension.
Primary pulmonary hypertension (PPH) is a rare and fatal disease of unknown etiology. Inflammatory oxidant mechanisms and deficiency in nitric oxide (NO) have been implicated in the pathogenesis of pulmonary hypertension. In order to investigate abnormalities in oxidants and antioxidants in PPH, we studied intrapulmonary NO levels, biochemical reaction products of NO, and antioxidants (glutathione [GSH], glutathione peroxidase [GPx], and superoxide dismutase [SOD]) in patients with PPH (n = 8) and healthy controls (n = 8). Intrapulmonary gases and fluids were sampled at bronchoscopy. Pulmonary hypertension was determined by right-heart catheterization. NO and biochemical reaction products of NO in the lung were decreased in PPH patients in comparison with healthy controls (NO [ppb] in airway gases: control, 8 +/- 1; PPH, 2.8 +/- 0. 9; p = 0.016; and NO products [microM] in bronchoalveolar lavage fluid [BALF]: control, 3.3 +/- 1.05; PPH, 0.69 +/- 0.21; p = 0.03). However, GSH in the lungs of PPH patients was higher than in those of controls (GSH [microM] in BALF: 0.55 +/- 0.04; PPH, 0.9 +/- 0.1; p = 0.015). SOD and GPx activities were similar in the two groups (p >/= 0.50). Biochemical reaction products of NO were inversely correlated with pulmonary artery pressures (R = -0.713; p = 0.047) and with years since diagnosis of PPH (R = -0.776; p = 0.023). NO reaction products are formed through interactions between oxidants and NO, with the end products of reaction dependent upon the relative levels of the two types of molecules. The findings of the study therefore show that NO and oxidant reactions in the lung are related to the increased pulmonary artery pressures in PPH.
Kaneko
F T
FT
Departments of Pulmonary and Critical Care Medicine and Cancer Biology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio, USA.
Arroliga
A C
AC
Dweik
R A
RA
Comhair
S A
SA
Laskowski
D
D
Oppedisano
R
R
Thomassen
M J
MJ
Erzurum
S C
SC
D000328:Adult; D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D001794:Blood Pressure / Q000502:physiology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D001999:Bronchoscopy; D006328:Cardiac Catheterization; D005122:Exudates and Transudates / Q000737:chemistry; D005260:Female; D005978:Glutathione / Q000032:analysis; D005979:Glutathione Peroxidase / Q000032:analysis; D006801:Humans; D006976:Hypertension, Pulmonary / Q000201:enzymology / Q000209:etiology / Q000378:metabolism*; D008168:Lung / Q000201:enzymology / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000032:analysis* / Q000097:blood / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism; D010084:Oxidation-Reduction; D011651:Pulmonary Artery; D013482:Superoxide Dismutase / Q000032:analysis; D013997:Time Factors
D000975:Antioxidants; D015415:Biomarkers; D016877:Oxidants; D009569:Nitric Oxide; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione