Effect of indomethacin on lung development in postnatal rats: possible role of prostaglandin in alveolar formation.

We administered 1.3 mg ip of indomethacin, a prostaglandin synthetase inhibitor, per 100 g body wt to male rat pups daily on postnatal days 4-13 and examined their lungs on day 14. Indomethacin administration produced abnormal lung structure with diminished alveolar air, increased alveolar duct air, increased mean linear intercept (gas-exchanging wall distance), diminished gas-exchanging surface area and surface-to-volume ratio, increased septal wall thickness, diminished the number of alveolar crests, and increased the number of lamellar bodies in alveolar type II cells. However, this procedure did not alter quantitative lung growth (normal lung weights, volumes, and DNA and protein contents). Tissue prostaglandin content was decreased. The total amount of lung collagen or elastin was unchanged, but when collagen was analyzed into soluble and insoluble components, soluble collagen was increased. Supplementation with 1.0 g of prostaglandin E2 per 100 g body wt to animals treated with indomethacin reduced the abnormalities in pulmonary architecture. We conclude that indomethacin affects lung structure in growing rats and that it is an unusual model in that lung growth is normal, but lung development is abnormal. We also suggest that prostaglandins may play a significant role in alveolar formation in postnatal lung development in rats.