title: Deficiency of lung antioxidants in idiopathic pulmonary arterial hypertension.
abstract: Idiopathic pulmonary arterial hypertension (IPAH) is associated with lower levels of the pulmonary vasodilator nitric oxide (NO) and its biochemical reaction products (nitrite [NO(2) (-)], nitrate [NO(3) (-)]), in part, due to the reduction in pulmonary endothelial NO synthesis. However, NO levels are also determined by consumptive reactions, such as with superoxide to form peroxynitrite, which subsequently may generate stable products of nitrotyrosine (Tyr-NO(2)) and/or NO(3) (-). In this context, superoxide dismutase (SOD) preserves NO in vivo by scavenging superoxide and preventing the consumptive reactions. Here, we hypothesized that reactive oxygen species (ROS) consumption of NO may contribute to the low NO level and development of pulmonary hypertension. To test this, nitrotyrosine and antioxidants glutathione (GSH), glutathione peroxidase (GPx), catalase, and SOD were evaluated in IPAH patients and healthy controls. SOD and GPx activities were decreased in IPAH lungs (all p < 0.05), while catalase and GSH activities were similar among the groups (all p > 0.2). SOD activity was directly related to exhaled NO (eNO) (R(2)= 0.72, p= 0.002), and inversely related to bronchoalveolar lavage (BAL) NO(3) (-) (R(2)=-0.73, p= 0.04). Pulmonary artery pressure (PAP) could be predicted by a regression model incorporating SOD, GPx, and NO(3) values (R(2)= 0.96, p= 0.01). These findings suggest that SOD and GPx are associated with alterations in NO and PAP in IPAH.
authors.affiliation: Department of Pathobiology, Lerner Research Institute, Cleveland Clinic Foundation, Ohio, USA.
authors.forename: Fares A
authors.initials: FA
authors.lastname: Masri
authors.forename: Suzy A A
authors.initials: SA
authors.lastname: Comhair
authors.forename: Iva
authors.initials: I
authors.lastname: Dostanic-Larson
authors.forename: Francisco Takao
authors.initials: FT
authors.lastname: Kaneko
authors.forename: Raed A
authors.initials: RA
authors.lastname: Dweik
authors.forename: Alejandro C
authors.initials: AC
authors.lastname: Arroliga
authors.forename: Serpil C
authors.initials: SC
authors.lastname: Erzurum
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000378:metabolism*; D001794:Blood Pressure; D001980:Bronchi / Q000201:enzymology / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology; D008168:Lung / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008954:Models, Biological; D009569:Nitric Oxide / Q000378:metabolism; D020545:Respiratory Mucosa / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000378:metabolism; D013599:Systole; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D000975:Antioxidants; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D013482:Superoxide Dismutase