Maternal nicotine effects on vascular endothelial growth factor expression and morphometry in rat lungs

Aims: Maternal smoking during pregnancy may impair pulmonary function in infants, and the exact mechanisms underlying these changes are unknown. We evaluated the effects of maternal nicotine exposure on lung VEGF expression and morphometry during the postnatal period in rats. Methods and results: Timed pregnant Sprague-Dawley rats were injected subcutaneously with nicotine at a dose of 2 mg/kg/day from Day 3 to Day 21 of gestation. A control group was injected with saline. Body weight, lung weight, and lung volume were comparable between control and nicotine-exposed rats. Plasma vascular endothelial growth factor (VEGF) levels and lung VEGF mRNA expression decreased with advancing age, and nicotine exposure insignificantly decreased plasma VEGF levels and lung VEGF mRNA expression, compared with the control rats during the study period. Nicotine exposure caused a significant decrease in vascular endothelial growth factor receptor (VEGFR)-2 mRNA expression, compared with the level of the control rats on Postnatal Day 1. On Postnatal Day 1, nicotine-exposed rats exhibited a significantly lower volume fraction of alveolar airspace and alveolar surface area and a significantly higher alveolar wall volume fraction than did the control rats. Conclusions: Maternal nicotine exposure during pregnancy decreases VEGF and VEGFR-2 mRNA expression and alters lung structure in the lungs of postnatal rats. Because angiogenesis is vital for alveolarization during normal lung development, these results suggest that decreased VEGF expression might be involved in the structural alterations of the developing lung after exposure to antenatal nicotine. (C) 2011 Elsevier Ireland Ltd. All rights reserved.