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.