PMID: 8959648Nov 1, 1996Paper

Inhibitory effect of indomethacin on neonatal lung catabolism of prostaglandin E2: possible mechanism of the re-opening of the ductus arteriosus after indomethacin therapy

The Journal of Toxicological Sciences
T TakizawaT Masaoka

Abstract

Indomethacin has been used to treat patent ductus arteriosus (PDA). Re-opening of the ductus arteriosus (DA) after indomethacin therapy, however, is common, although the reason is unclear. Patency of the ductus arteriosus is thought to be maintained primarily by the vasodilatory effect of PGE2 in fetuses and neonates. The enzyme, 15-hydroxy prostaglandin dehydrogenase (15-PGDH) catalyzes the initial reactions converting the biologically active PGE2 to its inactive metabolite 15-keto-PGE2, and the lungs are a major site of this inactivation. In the present study, the effect of prenatal indomethacin treatment on the activity of neonatal rat lung 15-PGDH, and the effect of prenatal indomethacin on the re-opening of the DA induced by PGE2 were examined in rats. Indomethacin treatment at 3 mg/kg/day from day 18 to day 20 of gestation significantly decreased the activity of 15-PGDH in neonatal lungs. In a subsequent experiment, subcutaneous injection of PGE2 (4 micrograms) was given to newborn rats 3 hr after Cesarean delivery from pregnant females administered indomethacin (1, 3 mg/kg/day) as in the above experiment. The ratio of the DA to pulmonary artery was determined at intervals after injection. Maternal indomethacin treatment ...Continue Reading

Citations

Jan 31, 2012·American Journal of Physiology. Lung Cellular and Molecular Physiology·Alana J WestoverTimothy J M Moss
Apr 30, 1998·The Journal of Veterinary Medical Science·T TakizawaT Masaoka

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