Constriction of the ductus arteriosus by selective inhibition of cyclooxygenase-1 and -2 in near-term and preterm fetal rats

Prostaglandins Other Lipid Mediat. 2006 Mar;79(1-2):34-42. doi: 10.1016/j.prostaglandins.2004.11.005.

Abstract

We studied the transplacental ductal constrictive effects of a selective cyclooxygenase (COX)-1 inhibitor (SC560), six selective COX-2 inhibitors including rofecoxib, and a non-selective COX inhibitor (indomethacin). Each drug was administered to the pregnant rats, and fetal ductus arteriosus (DA) was studied with a whole-body freezing method. The inner diameter ratio of the DA to the main pulmonary artery (DA/PA) was 1.02+/-0.03 (mean+/-S.E.M.) in controls. Every drug constricted the DA dose-dependently. In preterm rats on the 19th day of gestation, 10mg/kg of SC560, rofecoxib and indomethacin caused ductal constriction, with DA/PA reduced to 0.76+/-0.02, 0.80+/-0.03 and 0.75+/-0.02, respectively. In near-term on the 21st day, 10mg/kg of them caused ductal constriction, with DA/PA to 0.74+/-0.04, 0.26+/-0.02 and 0.33+/-0.05. In conclusion, both COX-1 and COX-2 selective inhibitors constrict fetal DA. They are not better alternatives for the fetus than non-selective COX inhibitors for tocolysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyclooxygenase 1 / metabolism
  • Cyclooxygenase 2 / metabolism
  • Cyclooxygenase Inhibitors / administration & dosage
  • Cyclooxygenase Inhibitors / adverse effects*
  • Dose-Response Relationship, Drug
  • Ductus Arteriosus, Patent / chemically induced
  • Ductus Arteriosus, Patent / enzymology
  • Ductus Arteriosus, Patent / physiopathology*
  • Female
  • Fetal Diseases / chemically induced
  • Fetal Diseases / enzymology
  • Fetal Diseases / physiopathology*
  • Fetus / abnormalities
  • Fetus / enzymology
  • Fetus / pathology
  • Fetus / physiopathology
  • Pregnancy
  • Rats
  • Rats, Wistar
  • Tocolysis / adverse effects*
  • Vasoconstriction / drug effects*

Substances

  • Cyclooxygenase Inhibitors
  • Cyclooxygenase 1
  • Cyclooxygenase 2