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DEVELOPMENT AND TISSUE PLASTICITY

Developmental regulation of prostaglandin E₂ synthase in porcine ductus arteriosus

¹Departments of Cardiology, Pediatrics, Physiology and Pharmacology, Ste-Justine Hospital Research Center, Université de Montréal, Montreal H3T 1C5; ²Theratechnologies, Montreal H4S 2A4; ⁴Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec H3G 1Y6, Canada; and ³Pediatrics, Cardiovascular Research Institute, University of California, San Francisco, California 94143

Submitted 4 August 2003 ; accepted in final form 5 January 2004

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.

platelet-activating factor; cyclooxygenase-2; cytosolic phospholipase A₂

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