Treatment of newborn rats with a VEGF receptor inhibitor causes pulmonary hypertension and abnormal lung structure

TD Le Cras, NE Markham, RM Tuder… - … of Physiology-Lung …, 2002 - journals.physiology.org
TD Le Cras, NE Markham, RM Tuder, NF Voelkel, SH Abman
American Journal of Physiology-Lung Cellular and Molecular …, 2002journals.physiology.org
To determine whether disruption of vascular endothelial growth factor (VEGF)-VEGF
receptor (VEGFR) signaling in the newborn has long-term effects on lung structure and
function, we injected 1-day-old newborn rat pups with a single dose of Su-5416, a VEGFR
inhibitor, or vehicle (controls). Lungs from infant (3-wk-old) and adult (3-to 4-mo-old) rats
treated with Su-5416 as newborns showed reductions in arterial density (82 and 31%,
respectively) and alveolar counts (45 and 29%) compared with controls. Neonatal treatment …
To determine whether disruption of vascular endothelial growth factor (VEGF)-VEGF receptor (VEGFR) signaling in the newborn has long-term effects on lung structure and function, we injected 1-day-old newborn rat pups with a single dose of Su-5416, a VEGFR inhibitor, or vehicle (controls). Lungs from infant (3-wk-old) and adult (3- to 4-mo-old) rats treated with Su-5416 as newborns showed reductions in arterial density (82 and 31%, respectively) and alveolar counts (45 and 29%) compared with controls. Neonatal treatment with Su-5416 increased right ventricle weight to body wt ratios (4.2-fold and 2.0-fold) and pulmonary arterial wall thickness measurements (2.7-fold and 1.6-fold) in infant and adult rats, respectively, indicating marked pulmonary hypertension. We conclude that treatment of newborn rats with the VEGFR inhibitor Su-5416 impaired pulmonary vascular growth and postnatal alveolarization and caused pulmonary hypertension and that these effects were long term, persisting well into adulthood.
American Physiological Society