A peroxynitrite decomposition catalyst prevents 60% O2-mediated rat chronic neonatal lung injury.
Exposure of newborn rats to 60% O2 for 14days results in a chronic neonatal lung injury characterized by parenchymal thickening, impaired alveolarization, evidence of pulmonary hypertension, and pulmonary vascular pruning. The contribution of peroxynitrite to this injury was assessed by treating pups with a peroxynitrite decomposition catalyst, 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrinato iron(III) chloride (FeTPPS), at 30microg/g/day. Body and lung weights and postfixation lung volumes were all slightly, but significantly, reduced by exposure to 60% O2 and this was attenuated by a concurrent FeTPPS intervention. The FeTPPS intervention had no impact on increased neutrophil or macrophage influx into the lung, but attenuated 60% O2-induced reductions in the lung contents of vascular endothelial-derived growth factor, its receptor-2, and angiopoietin and increases in 8-isoprostane and preproendothelin-1. The 60% O2-induced parenchymal thickening and impairment of alveologenesis, as well as vascular pruning and peripheral vessel medial wall thickening, were attenuated by FeTPPS, despite a persistent inflammatory cell influx. Pups exposed to 60% O2 and treated with FeTPPS had enhanced alveolar formation relative to control pups. We conclude that peroxynitrite plays a critical role in the development of chronic neonatal lung injury.
Masood
Azhar
A
Lung Biology Programme, Physiology & Experimental Medicine, Hospital for Sick Children Research Institute, Toronto, ON, M5G 1X8 Canada.
Belcastro
Rosetta
R
Li
Jun
J
Kantores
Crystal
C
Jankov
Robert P
RP
Tanswell
A Keith
AK
D042683:Angiopoietin-1 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002384:Catalysis; D006976:Hypertension, Pulmonary; D007150:Immunohistochemistry; D008168:Lung / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D055370:Lung Injury / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D008665:Metalloporphyrins / Q000008:administration & dosage* / Q000737:chemistry; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology; D010100:Oxygen / Q000008:administration & dosage; D030421:Peroxynitrous Acid / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism
C466420:5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrinato iron(III) chloride; D042683:Angiopoietin-1; D008665:Metalloporphyrins; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D030421:Peroxynitrous Acid; D040301:Vascular Endothelial Growth Factor Receptor-2; D010100:Oxygen