Developmental regulation of prostaglandin E2 synthase in porcine ductus arteriosus

1 Departments of Cardiology, Pediatrics, Physiology and Pharmacology, Ste-Justine Hospital Research Center, Université de Montréal, Montreal H3T 1C5; 2 Theratechnologies, Montreal H4S 2A4; 4 Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec H3G 1Y6, Canada; and 3 Pediatrics, Cardiovascular Research Institute, University of California, San Francisco, California 94143 Submitted 4 August 2003 ; accepted in final form 5 January 2004 The synthesis of PGE 2 , the major vasodilator prostanoid of the ductus arteriosus (DA), is catalyzed by PGE 2 synthases (PGES). The factors implicated in increased PGE 2 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 A 2 (cPLA 2 ) in the DA of fetal (75-90% gestation) and immediately postnatal newborn (NB) piglets. Levels of microsomal PGES (mPGES), COX-2, and PGE 2 in the DA of NB were 7-fold higher than in fetus; activities of cytosolic PGES (cPGES) and cPLA 2 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 PGE 2 in fetal DA to levels approaching those of the NB; cPGES, cPLA 2 , and COX-1 were unaffected. In perinatal NB DA, PAF receptor antagonists BN-52021 and THG-315 reduced mPGES, COX-2, and PGE 2 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 PGE 2 levels in the perinate. platelet-activating factor; cyclooxygenase-2; cytosolic phospholipase A 2 Address for reprint requests and other correspondence: S. Chemtob, FRCP(C), Research Center, Ste-Justine Hospital, 3175 Côte Ste-Catherine, Montréal, Quebec H3T 1C5, Canada (E-mail: sylvain.chemtob{at}umontreal.ca ).