Studies on closure of the ductus arteriosus. XII. In utero effect of indomethacin and sodium salicylate in rats and rabbits

Prostaglandins. 1975 Apr;9(4):585-96. doi: 10.1016/0090-6980(75)90064-7.

Abstract

Administration of prostaglandin synthetase inhibitors to pregnant does and dams in late gestation was followed by in utero contraction of the fetal ductus arteriosus when studied by the whole-body freezing method. In the rat this contraction was well established within 6 h and persisted up to 36 h following 15 mg/kg indomethacin p.o. No effect was observed in the 18 d rat fetus but fetuses at 20 d and 22 d of gestation responded significantly to indomethacin. Doses of indomethacin approaching clinical usage (2.5 mg/kg also caused a positive response in utero. The rat was found to be sensitive also to sodium salicylate and in the rabbit both indomethacin and sodium salicylate were effective. Exposure in utero to prostaglandin synthetase inhibitors with resulting contraction of the ductus may seriously disturb cardiac function in the fetus.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Cyclooxygenase Inhibitors
  • Depression, Chemical
  • Dose-Response Relationship, Drug
  • Ductus Arteriosus / anatomy & histology
  • Ductus Arteriosus / drug effects*
  • Female
  • Gestational Age
  • Indomethacin / administration & dosage
  • Indomethacin / pharmacology*
  • Male
  • Mice
  • Muscle Contraction / drug effects*
  • Pregnancy
  • Rabbits
  • Rats
  • Sodium Salicylate / administration & dosage
  • Sodium Salicylate / pharmacology*
  • Stimulation, Chemical
  • Time Factors

Substances

  • Cyclooxygenase Inhibitors
  • Sodium Salicylate
  • Indomethacin