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Role of prostaglandin E 2 and its receptors in the process of ductus arteriosus maturation and functional closure in the rabbit
Author(s) -
Fan FenLing,
Zhu Sen,
Chen LiHong,
Zou YuLiang,
Fan LiHong,
Kang JiHong,
Ma AiQun,
Guan YouFei
Publication year - 2010
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2010.05354.x
Subject(s) - ductus arteriosus , receptor , vasoconstriction , medicine , endocrinology , prostaglandin , prostaglandin e , chemistry
Summary 1. Patent ductus arteriosus (PDA) is a common congenital heart defect in premature infants. The present study was designed to determine the role of the prostaglandin (PG) E 2 pathway in the process of ductus arteriosus (DA) maturation and functional closure. 2. Changes in PGE 2 pathway‐related enzymes and receptors in DA in preterm and term rabbits were examined at both the mRNA and protein levels. In addition, responses of DA rings to P o 2 and PGE 2 were determined. 3. Circulating PGE 2 levels remained high until 2 h after birth. High levels of the EP 4 receptor were found in preterm DA. These tissues were sensitive to PGE 2 , which caused vessel dilation, but were insensitive to increased P o 2 . In contrast, DA tissues from term rabbits exhibited an immediate contractile response to increased P o 2 and PGE 2 treatment resulted in vasoconstriction, which was associated with increased EP 3 and decreased EP 4 receptor expression in term DA. 4. In conclusion, the preterm PDA is maintained by high levels of PGE 2 , which mainly binds to the EP 4 receptor under conditions of hypoxia. In contrast, in the term DA, in which levels of the EP 3 receptor are higher than in preterm DA, exposure to PGE 2 resulted in vasoconstriction under normoxic conditions. These findings suggest that blocking the EP 4 receptor may represent a more selective treatment for the preterm PDA, whereas activating the EP 3 receptor may be more suitable for the treatment of the term PDA.