title: Time course for expression of VEGF and its receptor and regulator levels of contraction and relaxation in increased vascular permeability of lung induced by phosgene.
abstract: Acute lung injury (ALI) induced by phosgene increases risk of serious edema and mortality. Increased permeability of the microvascular endothelium is implicated in the progression of ALI, but the processing interaction and time course activity of the vascular regulators in exudation are still not understood. The main aim of this study was to investigate the time course and potential role for vascular endothelial growth factor (VEGF), its receptors, and some vascular function regulators related to increased vascular permeability of lung induced by phosgene. Sprague Dawley rats were randomly divided into seven groups according to time post phosgene exposure (control, and 1, 3, 6, 12, 24, and 48 h groups). Lung tissue was removed to evaluate VEGF isoforms, fms-like tyrosine kinase receptor 1 (Flt-1), and kinase insert domain containing region (KDR/Flk-1) by reverse-transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Blood samples were collected for measurement of plasma endothelin-1 (ET-1) and nitric oxide (NO) level. The results showed that the mRNA and protein expression profile of the VEGF system after phosgene exposure was time dependent. The VEGF system expression in lung tissue was related closely to the level of ET-1 and NO. In conclusion, increased permeability of the lung microvascular endothelium induced by phosgene was primarily a result of differential expression of VEGF and its receptors, and was related to the level of ET-1 and NO. The results suggest that the cooperation of VEGF system, ET-1, and NO plays a critical role, and all those parameters emerge as time dependent in the early phase of the permeability process induced by phosgene exposure.
authors.affiliation: Department of Toxicology, The Fourth Military Medical University, Xi'an, People's Republic of China.
authors.forename: Xiao-di
authors.initials: XD
authors.lastname: Zhang
authors.forename: Chun-Xu
authors.initials: CX
authors.lastname: Hai
authors.forename: Feng-Lei
authors.initials: FL
authors.lastname: Cai
authors.forename: Xin
authors.initials: X
authors.lastname: Liang
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.forename: Hong-Li
authors.initials: HL
authors.lastname: Chen
authors.forename: Xu-Jun
authors.initials: XJ
authors.lastname: Qin
authors.forename: An-Ji
authors.initials: AJ
authors.lastname: Feng
mesh_terms: D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D002619:Chemical Warfare Agents / Q000633:toxicity*; D019332:Endothelin-1 / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects / Q000648:ultrastructure; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression / Q000187:drug effects; D008168:Lung / Q000098:blood supply / Q000187:drug effects*; D008171:Lung Diseases / Q000097:blood / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000648:ultrastructure; D009569:Nitric Oxide / Q000097:blood; D010705:Phosgene / Q000633:toxicity*; D011652:Pulmonary Circulation / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D040262:Receptors, Vascular Endothelial Growth Factor / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism
chemical_list: D002619:Chemical Warfare Agents; D019332:Endothelin-1; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D010705:Phosgene; D009569:Nitric Oxide; C501164:Flt1 protein, rat; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2