Inducible nitric oxide synthase inhibition attenuates lung tissue responsiveness and remodeling in a model of chronic pulmonary inflammation in guinea pigs.
We evaluated the influence of iNOS-derived NO on the mechanics, inflammatory, and remodeling process in peripheral lung parenchyma of guinea pigs with chronic pulmonary allergic inflammation. Animals treated or not with 1400 W were submitted to seven exposures of ovalbumin in increasing doses. Seventy-two hours after the 7th inhalation, lung strips were suspended in a Krebs organ bath, and tissue resistance and elastance measured at baseline and after ovalbumin challenge. The strips were submitted to histopathological measurements. The ovalbumin-exposed animals showed increased maximal responses of resistance and elastance (p<0.05), eosinophils counting (p<0.001), iNOS-positive cells (p<0.001), collagen and elastic fiber deposition (p<0.05), actin density (p<0.05) and 8-iso-PGF2alpha expression (p<0.001) in alveolar septa compared to saline-exposed ones. Ovalbumin-exposed animals treated with 1400 W had a significant reduction in lung functional and histopathological findings (p<0.05). We showed that iNOS-specific inhibition attenuates lung parenchyma constriction, inflammation, and remodeling, suggesting NO-participation in the modulation of the oxidative stress pathway.
Starling
Claudia M
CM
Department of Medicine, School of Medicine, University of São Paulo, Av. Dr. Arnaldo, 455, Sala 1216, 01246-903 São Paulo, SP, Brazil.
Prado
Carla M
CM
Leick-Maldonado
Edna A
EA
Lanças
Tatiana
T
Reis
Fabiana G
FG
Aristóteles
Luciana R C B R
LR
Dolhnikoff
Marisa
M
Martins
Mílton A
MA
Tibério
Iolanda F L C
IF
D000199:Actins / Q000378:metabolism; D000818:Animals; D002908:Chronic Disease; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D004548:Elasticity; D004804:Eosinophils / Q000166:cytology; D005109:Extracellular Matrix / Q000276:immunology / Q000378:metabolism; D006168:Guinea Pigs; D028421:Isoprostanes / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology; D018384:Oxidative Stress / Q000276:immunology*; D011014:Pneumonia / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000276:immunology / Q000378:metabolism
D000199:Actins; D028421:Isoprostanes; D009569:Nitric Oxide; D010047:Ovalbumin; D003094:Collagen; D052247:Nitric Oxide Synthase Type II