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Am J Physiol Regul Integr Comp Physiol (January 8, 2004). doi:10.1152/ajpregu.00437.2003
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Submitted on August 4, 2003
Accepted on January 5, 2004

Developmental regulation of prostaglandin E2 synthase in porcine ductus arteriosus

Asmaa Bouayad1, Jean-Claude Fouron1, Xin Hou1, Martin Beauchamp1, Christiane Quiniou1, Daniel Abran2, Krishna Peri2, Ronald I Clyman3, Daya R Varma4, and Sylvain Chemtob5*

1 Departments of Cardiology, Pediatrics, Physiology and Pharmacology, University of Montreal, Ste-Justine Hospital, Montreal, Quebec, Canada
2 Theratechnologies Inc., Montreal, Quebec, Canada
3 Pediatrics, Cardiovascular Research Institute, UCSF, San Fransisco, CA, USA
4 Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada
5 Departments of Cardiology, Pediatrics, Physiology and Pharmacology, University of Montreal, Ste-Justine Hospital, Montreal, Quebec, Canada; Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada

* To whom correspondence should be addressed. E-mail: sylvain.chemtob{at}umontreal.ca.

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 PGE2 synthases (PGES) along with that of cyclooxygenase (COX)-2 and cytosolic phospholipase A2 (cPLA2) in the DA of fetal (75-90% gestation) and immediately post-natal newborn (NB) piglets. Levels of microsomal PGES (mPGES), COX-2 and PGE2 in the DA of NB were approximately 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, BN52021 and THG315, reduced mPGES, COX-2 and PGE2 levels, and was 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.




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