Elevated immunoreactive endothelin-1 levels in newborn rabbit lungs after meconium aspiration.

Abstract

OBJECTIVE: Our prime objective was to study the production of big endothelin-1 (Big ET-1) and its conversion to ET-1 in the lungs of newborn rabbits exposed to meconium. Our second objective was to study the effect of captopril on endothelin expression. DESIGN: Prospective, comparative study. SETTING: Research laboratory of the Michael Reese Hospital and the University of Illinois, Chicago. SUBJECTS: Two-wk-old rabbit pups. INTERVENTIONS: Rabbit pups were instilled with meconium or saline into the lungs. Another group, pretreated with captopril, was also instilled with either meconium or saline. MEASUREMENTS AND MAIN RESULTS: After meconium or saline instillation, lung lavage was performed. Big ET-1 and ET-1 were measured in lung lavage fluid by using a commercially available enzyme-linked immunosorbent assay kits in all groups. Also, lungs were studied by histochemistry analysis for a morphologic evaluation of meconium-induced damage. In the lavage fluid of saline-instilled pups, ET-1 remained low and no increase in Big ET-1 levels was observed. In meconium-instilled animals, bioactive ET-1 levels were significantly higher, with a peak at 8 hrs after instillation. The conversion ratio of Big ET-1 to ET-1 in the meconium group increased from 2.19 at the initial period to 7.19 at 8 hrs after meconium instillation. CONCLUSIONS: Our conclusion is that aspiration of meconium causes lung injury in the newborn and that this injury is associated with a significant increase in ET peptide production in the lungs. We also showed that ET production is inhibited by pretreatment of rabbits with captopril before meconium-induced injury. ET-1 and its conversion from ET-1 in response to meconium may play important roles in increasing pulmonary vascular resistance and lung cell death, even in the absence of hypoxia. In general, we conclude, that ET-1 levels are significantly elevated in meconium-instilled rabbits compared with saline-instilled ones, and both can be significantly inhibited by pretreatment with captopril. Whether ET-1 contributes directly to the pathophysiology of or is simply a marker of meconium aspiration syndrome remains speculative.