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

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, 10 mg/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, 10 mg/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.