467 EFFECT OF INDOMETHACIN AND IBUPROFEN ON RAT LUNG VASCULAR ENDOTHELIAL GROWTH FACTOR AND SOLUBLE VASCULAR ENDOTHELIAL GROWTH FACTOR RECEPTORS DURING EARLY POSTNATAL DEVELOPMENT.

Vascular endothelial growth factor (VEGF) is a potent endothelial cell mitogen that is highly involved in lung microvasculature proliferation, permeability, and maturation. Its overexpression in the neonatal lung results in pulmonary hemorrhage and inflammation. Soluble VEGF receptors (sVEGFR-1, sVEGFR-2) are the negative regulators in the VEGF signaling pathway. Indomethacin (Indo) is administered to premature newborn infants for ductus arteriosus closure. However, its use is associated with increased pulmonary vascular resistance. The purpose of this study was to compare the effects of early administration of Indo and Ibu on VEGF and its soluble receptors in the developing rat lungs. Sprague-Dawley rats received IP injections at birth (P0), postnatal day 1 (P1), and P2 of either saline (Sal); 0.2 mg/kg IN on P0 followed by 0.1 mg/kg on P1 and P2; 1.0 mg/kg IN on P0 followed by 0.5 mg/kg on P1 and P2; 10 mg/kg IB on P0 followed by 5 mg/kg on P1 and P2; and 50 mg/kg IB on P0 followed by 25 mg/kg on P1 and P2. At P14 and P21 (time of microvascular maturation), lung homogenates were assessed for VEGF, sVEGFR-1 and sVEGFR-2. Untreated term rat lungs were also examined. VEGF levels increased at P14 and P21 ( p