Nitric oxide and superoxide anion balance in rats exposed to chronic and long term intermittent hypoxia.
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.
Instituto de Estudios de la Salud, Universidad Arturo Prat, Avenida Arturo Prat 2120, 11100939 Iquique, Chile.
Patricia
P
Siques
Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid, 28029 Madrid, Spain ; Instituto de Investigación Hospital Universitario Gregorio Marañón, 28007 Madrid, Spain.
Angel Luis
AL
López de Pablo
Instituto de Estudios de la Salud, Universidad Arturo Prat, Avenida Arturo Prat 2120, 11100939 Iquique, Chile.
Julio
J
Brito
Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid, 28029 Madrid, Spain ; Instituto de Investigación Hospital Universitario Gregorio Marañón, 28007 Madrid, Spain.
Silvia M
SM
Arribas
Instituto de Estudios de la Salud, Universidad Arturo Prat, Avenida Arturo Prat 2120, 11100939 Iquique, Chile.
Karen
0000-0003-2853-4461
K
Flores
Instituto de Estudios de la Salud, Universidad Arturo Prat, Avenida Arturo Prat 2120, 11100939 Iquique, Chile.
Karem
0000-0003-1498-5579
K
Arriaza
Instituto de Estudios de la Salud, Universidad Arturo Prat, Avenida Arturo Prat 2120, 11100939 Iquique, Chile.
Nelson
N
Naveas
Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid, 28029 Madrid, Spain ; Instituto de Investigación Hospital Universitario Gregorio Marañón, 28007 Madrid, Spain.
M Carmen
MC
González
Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid, 28029 Madrid, Spain.
Alexander
0000-0002-4268-9526
A
Hoorntje
Departamento de Ciencias Biológicas y Fisiológicas, Facultad de Ciencias y Filosofía/IIA, Universidad Peruana Cayetano Heredia, Lima 31, Lima, Peru.
Fabiola
F
León-Velarde
Departamento de Medicina Preventiva, Salud Pública y Microbiología, Facultad de Medicina, Universidad Autónoma de Madrid, 28029 Madrid, Spain.
M Rosario
MR
López
D000818:Animals; D017380:Hypertrophy, Right Ventricular / Q000378:metabolism* / Q000473:pathology; D000860:Hypoxia / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D000074624:NADPH Oxidase 1; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D011651:Pulmonary Artery / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000378:metabolism*
D013481:Superoxides; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D009247:NADH, NADPH Oxidoreductases; D000074624:NADPH Oxidase 1