[Dynamic changes in vascular endothelial growth factor and endothelial nitric oxide synthase in lungs of premature rats after hyperoxia exposure].

OBJECTIVE

Recent studies suggest that the disruption of vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) functions plays a pivotal role in the pathogenesis of bronchopulmonary dysplasia (BPD). The aim of this study was to investigate the changes of VEGF and eNOS expression in the lungs of premature rats exposed to moderate hyperoxia in order to explore possible relationships with BPD.

METHODS

Premature rats delivered by hysterotomy at 21 days gestation were randomly continuously exposed to moderate hyperoxia (60% FiO2) and room air. The rats were sacrificed at 1, 4, 7, 11 and 14 days of exposure (6 rats at each time point). Lung sections were stained with hematoxylin and eosin for histological examination. Expression of VEGF and eNOS proteins and mRNA were assayed using immunohistochemistry and RT-PCR.

RESULTS

After 4 days of hyperoxia, lungs developed interstitial fibrosis, abnormal vascular patterns and decreased alveolar septation. These changes became more obvious with more prolonged hyperoxia exposure. The expression of VEGF protein after 4 and 7 days of exposure decreased significantly in the hyperoxia group compared with controls. The expression of VEGF mRNA in the hyperoxia group was also lower after 4 and 7 days of exposure. Both VEGF protein and mRNA levels decreased with increasing hyperoxia exposure time. The expressions of eNOS protein and mRNA also progressively decreased with increasing hyperoxia exposure.

CONCLUSIONS

Hyperoxia caused progressive reduction in lung VEGF and eNOS expression as well as abnormalities of lung structures, including decreased vascular growth and impaired alveolarization. These histologic changes are similar to those of BPD. The data support a link between BPD and decreased expression of VEGF and eNOS.