The synthesis of PGE2, the major vasodilator prostanoid of the ductus arteriosus (DA), is catalyzed by PGE2 synthases (PGES). The factors implicated in increased PGE2 synthesis in the perinatal DA are not known. We studied the developmental changes of PGES along with that of cyclooxygenase (COX)-2 and cytosolic phospholipase A2 (cPLA2) in the DA of fetal (75-90% gestation) and immediately postnatal newborn (NB) piglets. Levels of microsomal PGES (mPGES), COX-2, and PGE2 in the DA of NB were ∼7-fold higher than in fetus; activities of cytosolic PGES (cPGES) and cPLA2 in DA of the fetus and NB did not differ. Because platelet-activating factor (PAF) could regulate COX-2 expression, the former was measured and found to be more abundant in the DA of the NB than of fetus. PAF elicited an increase in mPGES, COX-2, and PGE2 in fetal DA to levels approaching those of the NB; cPGES, cPLA2, and COX-1 were unaffected. In perinatal NB DA, PAF receptor antagonists BN-52021 and THG-315 reduced mPGES, COX-2, and PGE2 levels and were associated with increased DA tone. It is concluded that PAF contributes in regulating DA tone by governing mPGES, COX-2, and ensuing PGE2 levels in the perinate.
Developmental Changes in PGE2 Receptor Subtypes in Porcine Ductus Arteriosus: Possible Contribution in Altered Responsiveness to PGE2
