Exposure to hyperoxia decreases the expression of vascular endothelial growth factor and its receptors in adult rat lungs

Exposure to high levels of inspired oxygen leads to respiratory failure and death in many animal models. Endothelial cell. death is an early finding, before the onset of respiratory failure. Vascular endothelial growth factor (VEGF) is highly expressed in the lungs of adult animals. In the present s tudy, adult Sprague-Dawley rats were exposed to >95% FiO(2) for 24 or 48 ho urs. Northern blot analysis revealed a marked reduction in VEGF mRNA abunda nce by 24 hours, which decreased to less than 50% of control by 48 hours. I n situ hybridization revealed that VEGF was highly expressed in distal airw ay epithelial cells in controls but disappeared in the oxygen-exposed anima ls. Immunohistochemistry and Western blot analyses demonstrated that VEGF p rotein was decreased at 48 hours. TUNEL staining demonstrated the presence of apoptotic cells coincident with the decline in VEGF. Abundance of VEGF r eceptor mRNAs (Flt-1 and KDR/Flk) decreased in the late time points of the study (48 hours), possibly secondary to the loss of endothelial cells. We s peculate that VEGF functions as a survival factor in the normal adult rat l ung, and its loss during hyperoxia contributes to the pathophysiology of ox ygen-induced lung damage.