Nitric Oxide and Superoxide Anion Balance in Rats Exposed to Chronic and Long Term Intermittent Hypoxia

• Published in: BioMed research international Vol. 2014; no. 2014; pp. 1 - 10
• Main Authors: Siques, Patricia, López de Pablo, Ángel Luis, Brito, Julio, Arribas, Silvia M., Flores, Karen, Arriaza, Karem, Naveas, Nelson, González, María Carmen, Hoorntje, Alexander, León-Velarde, Fabiola, López, M. Rosario
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Puplishing Corporation 01.01.2014; Hindawi Publishing Corporation; John Wiley & Sons, Inc; Hindawi Limited
• Subjects: Animals; Hypertrophy, Right Ventricular - metabolism; Hypertrophy, Right Ventricular - pathology; Hypoxia; Hypoxia - metabolism; Hypoxia - pathology; Immunohistochemistry; Male; NADH, NADPH Oxidoreductases - metabolism; NADPH Oxidase 1; Nitric oxide; Nitric Oxide - metabolism; Nitric Oxide Synthase Type III - metabolism; Pulmonary arteries; Pulmonary Artery - metabolism; Pulmonary Artery - pathology; Pulmonary hypertension; Rats; Rats, Wistar; Rodents; Sea level; Studies; Superoxide; Superoxides - metabolism; Veins & arteries; Spain
• ISSN: 2314-6133; 2314-6141
• DOI: 10.1155/2014/610474

Work at high altitude in shifts exposes humans to a new form of chronic intermittent hypoxia, with still unknown health consequences. We have established a rat model resembling this situation, which develops a milder form of right ventricular hypertrophy and pulmonary artery remodelling compared to continuous chronic exposure. We aimed to compare the alterations in pulmonary artery nitric oxide (NO) availability induced by these forms of hypoxia and the mechanisms implicated. Rats were exposed for 46 days to normoxia or hypobaric hypoxia, either continuous (CH) or intermittent (2 day shifts, CIH2x2), and assessed: NO and superoxide anion availability (fluorescent indicators and confocal microscopy); expression of phosphorylated endothelial NO synthase (eNOS), NADPH-oxidase (p22phox), and 3-nitrotyrosine (western blotting); and NADPH-oxidase location (immunohistochemistry). Compared to normoxia, (1) NO availability was reduced and superoxide anion was increased in both hypoxic groups, with a larger effect in CH, (2) eNOS expression was only reduced in CH, (3) NADPH-oxidase was similarly increased in both hypoxic groups, and (4) 3-nitrotyrosine was increased to a larger extent in CH. In conclusion, intermittent hypoxia reduces NO availability through superoxide anion destruction, without reducing its synthesis, while continuous hypoxia affects both, producing larger nitrosative damage which could be related to the more severe cardiovascular alterations.