Meconium aspiration stimulates cyclooxygenase-2 and nitric oxide synthase-2 expression in rat lungs.

To study the impact of meconium aspiration on the biosynthesis of prostaglandins and nitric oxide, we investigated the effects of intratracheal meconium instillation on the expression of cyclooxygenase-1 (COX-1) and -2 (COX-2) and endothelial (NOS-3) and inducible (NOS-2) nitric oxide synthase in rat lungs. Anesthetized, tracheotomized, and ventilated rats received 3 mL/kg human meconium suspension intratracheally (n = 19), and 14 control rats received an equal volume of saline. Ten rats were pretreated with indomethacin, and 13 rats were pretreated with dexamethasone. The lungs were ventilated with 70% oxygen for 3 h after the insult, and the level of COX-1, COX-2, NOS-2, and NOS-3 mRNA in lung tissue was analyzed by Northern blot hybridization. Furthermore, the expression and localization of the enzyme proteins was analyzed by immunohistochemistry. COX-1 and NOS-3 were clearly expressed in the lungs of control rats, whereas the level of COX-2 and NOS-2 expression was minimal. Meconium administration did not affect the expression of COX-1, but COX-2 expression was up-regulated in the respiratory epithelium and alveolar macrophages. Meconium also induced up-regulation of NOS-2 in the pulmonary epithelium, vascular endothelium, and macrophages. Indomethacin pretreatment did not affect the enzyme expressions, whereas dexamethasone administration significantly inhibited the meconium-induced COX-2 and NOS-2 up-regulation. Our data thus indicate that intrapulmonary meconium up-regulates lung COX-2 and NOS-2 gene expression, suggesting an important role for prostaglandins and nitric oxide in the meconium aspiration-induced pulmonary inflammation and hemodynamic changes.