Comparison of effects of cyclooxygenase inhibitors on myometrial contraction and constriction of ductus arteriosus in rats

Abstract

The aim of this study was to compare the tocolytic effect of a selective cylooxygenase-2 inhibitor, DFU (5,5-dimethyl-3(3-fluorophenyl)4-(4-methylsulphonyl)phenyl-2(5H)-furanone), indomethacin and nimesulide on myometrial strips isolated from rats in both lipopolysaccharide-induced preterm labour and term labour. We also compared the constrictor effects of DFU and indomethacin on the fetal ductus arteriosus. Myometrial strips were obtained from preterm and term labour Wistar albino rats and were mounted in organ baths for the recording of isometric tension. DFU, nimesulide and indomethacin significantly inhibited KCl-, oxytocin-, prostaglandin E-2- and prostaglandin F-2alpha-stimulated contractions of myometrial strips isolated from rats in preterm and term labour. The E-max value of indomethacin was significantly lower than those for DFU and nimesulide (P<0.05), with no change-log (10) EC50 values. There was no significant difference between in -log (10) EC50 and E-max values of DFU and nimesulide for any of the tissues (P>0.05). In addition, there was no significant difference between - log (10) EC50 and E-max values for each of these three agents in myometrial tissues isolated from rats in preterm and term labour (P>0.05). Fetal ductus arteriosus was significantly constricted by DFU (10 or 100 mg/kg) in preterm and term rats, although DFU (10 or 100 mg/kg)-induced constriction ratios were significantly lower than those for indomethacin (P<0.05). These data demonstrate that DFU, a specific cyclooxygenase-2 inhibitor, could be considered as a new therapeutic agent for preterm labour. However, careful attention should be given to constriction of the fetal ductus arteriosus. (C) 2003 Elsevier B.V. All rights reserved.