Role of prostaglandin E and its receptors in the process of ductus arteriosus maturation and functional closure in the rabbit.
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 Po(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 Po(2). In contrast, DA tissues from term rabbits exhibited an immediate contractile response to increased Po(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.
Fan
Fen-Ling
FL
Department of Cardiovascular Medicine, The Key Laboratory of Environment and Gene-related Diseases, The Ministry of Education, Center of Cardiovascular Medicine of Xi'an Jiaotong University, Xi'an 710061, China.
Zhu
Sen
S
Chen
Li-Hong
LH
Zou
Yu-Liang
YL
Fan
Li-Hong
LH
Kang
Ji-Hong
JH
Ma
Ai-Qun
AQ
Guan
You-Fei
YF
D000818:Animals; D000831:Animals, Newborn; D015232:Dinoprostone / Q000097:blood / Q000494:pharmacology / Q000502:physiology*; D004373:Ductus Arteriosus / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004374:Ductus Arteriosus, Patent / Q000097:blood / Q000201:enzymology / Q000209:etiology / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005865:Gestational Age; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D010100:Oxygen / Q000494:pharmacology; D010957:Plasmids; D011247:Pregnancy; D047928:Premature Birth / Q000097:blood / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D011817:Rabbits; D018078:Receptors, Prostaglandin E / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014661:Vasoconstriction / Q000187:drug effects
D018078:Receptors, Prostaglandin E; D012313:RNA; D015232:Dinoprostone; D010100:Oxygen