Expression of cyclooxygenases in ductus arteriosus of fetal and newborn pigs

OBJECTIVE: We studied the ontogeny of the expression of cyclooxygenase- 1 and cyclooxygenase-2 in the ductus arteriosus and evaluated their functional significance. STUDY DESIGN: The expression of cyclooxygenase-1 and cyclooxygenase-2 was studied in ductus arteriosus of fetal (at ~75% gestation) and term newborn pig. Effects of selective inhibitors of cyclooxygenase-1 and cyclooxygenase-2 on ductal patency were evaluated by Doppler ultrasonography. RESULTS: Ductus arteriosus of the fetus expressed virtually only cyclooxygenase-1 immunoreactive protein and activity. In contrast, the ductus of the term newborn pig (<45 minutes old) contained proteins of both cyclooxygenase-1 and cyclooxygenase-2, but the latter contributed to >90% of prostaglandin E₂ formation. The selective cyclooxygenase-2 inhibitor DuP697 reduced prostaglandin E₂ levels in the ductus arteriosus, albeit not in plasma, but did not affect ductal patency in the newborn pig (<1 1/2 hours old); in contrast, the cyclooxygenase-1 inhibitor valeryl salicylate, like indomethacin, markedly reduced levels of prostaglandin E₂ in the plasma and ductus arteriosus and caused significant constriction of the ductus arteriosus. CONCLUSION: The ductus arteriosus of the term newborn pig, in contrast to that of the fetus, expresses cyclooxygenase-2, but circulating prostaglandins, arising mostly from cyclooxygenase-1, seem to exert the major control on ductal patency in vivo. Our data suggest that cyclooxygenase-2 inhibitors might be better alternatives for the fetus than nonselective cyclooxygenase blockers if indicated for maternal conditions such as inflammation or for tocolysis.