Isoprostanes as physiological mediators of transition to newborn life: Novel mechanisms regulating patency of the term and preterm ductus arteriosus

Jian Xiong Chen, Patrick W. O'Mara, Stanley D. Poole, Naoko Brown, Noah J. Ehinger, James C. Slaughter, Bibhash C. Paria, Judy L. Aschner, Jeff Reese

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Background: Increased oxygen tension at birth regulates physiologic events that are essential to postnatal survival, but the accompanying oxidative stress may also generate isoprostanes. We hypothesized that isoprostanes regulate ductus arteriosus (DA) function during postnatal vascular transition. Methods: Isoprostanes were measured by gas chromatography-mass spectrometry. DA tone was assessed by pressure myography. Gene expression was measured by quantitative PCR. Results: Oxygen exposure was associated with increased 8-iso-prostaglandin (PG)F2α in newborn mouse lungs. Both 8-iso-PGE2 and 8-iso-PGF2α induced concentration-dependent constriction of the isolated term DA, which was reversed by the thromboxane A2 (TxA2) receptor antagonist SQ29548. SQ29548 pretreatment unmasked an isoprostane-induced DA dilation mediated by the EP4 PG receptor. Exposure of the preterm DA to 8-iso-PGE2 caused unexpected DA relaxation that was reversed by EP4 antagonism. In contrast, exposure to 8-iso-PGF2α caused preterm DA constriction via TxA2 receptor activation. Further investigation revealed the predominance of the TxA2 receptor at term, whereas the EP4 receptor was expressed and functionally active from mid-gestation onward. Conclusion: This study identifies a novel physiological role for isoprostanes during postnatal vascular transition and provide evidence that oxidative stress may act on membrane lipids to produce vasoactive mediators that stimulate physiological DA closure at birth or induce pathological patency of the preterm DA.

Original languageEnglish (US)
Pages (from-to)122-128
Number of pages7
JournalPediatric Research
Volume72
Issue number2
DOIs
StatePublished - Aug 2012
Externally publishedYes

Fingerprint

Isoprostanes
Ductus Arteriosus
Prostaglandin H2 Receptors Thromboxane A2
Dinoprost
Constriction
Blood Vessels
Receptors, Prostaglandin E, EP4 Subtype
Oxidative Stress
Myography
Parturition
Oxygen
Patent Ductus Arteriosus
Membrane Lipids
Gas Chromatography-Mass Spectrometry
Dilatation
Gene Expression
Pressure
Pregnancy
Polymerase Chain Reaction
Lung

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Isoprostanes as physiological mediators of transition to newborn life : Novel mechanisms regulating patency of the term and preterm ductus arteriosus. / Chen, Jian Xiong; O'Mara, Patrick W.; Poole, Stanley D.; Brown, Naoko; Ehinger, Noah J.; Slaughter, James C.; Paria, Bibhash C.; Aschner, Judy L.; Reese, Jeff.

In: Pediatric Research, Vol. 72, No. 2, 08.2012, p. 122-128.

Research output: Contribution to journalArticle

Chen, JX, O'Mara, PW, Poole, SD, Brown, N, Ehinger, NJ, Slaughter, JC, Paria, BC, Aschner, JL & Reese, J 2012, 'Isoprostanes as physiological mediators of transition to newborn life: Novel mechanisms regulating patency of the term and preterm ductus arteriosus', Pediatric Research, vol. 72, no. 2, pp. 122-128. https://doi.org/10.1038/pr.2012.58
Chen, Jian Xiong ; O'Mara, Patrick W. ; Poole, Stanley D. ; Brown, Naoko ; Ehinger, Noah J. ; Slaughter, James C. ; Paria, Bibhash C. ; Aschner, Judy L. ; Reese, Jeff. / Isoprostanes as physiological mediators of transition to newborn life : Novel mechanisms regulating patency of the term and preterm ductus arteriosus. In: Pediatric Research. 2012 ; Vol. 72, No. 2. pp. 122-128.
@article{f76f9d3bcdff45a79cda9152bb4b6b7d,
title = "Isoprostanes as physiological mediators of transition to newborn life: Novel mechanisms regulating patency of the term and preterm ductus arteriosus",
abstract = "Background: Increased oxygen tension at birth regulates physiologic events that are essential to postnatal survival, but the accompanying oxidative stress may also generate isoprostanes. We hypothesized that isoprostanes regulate ductus arteriosus (DA) function during postnatal vascular transition. Methods: Isoprostanes were measured by gas chromatography-mass spectrometry. DA tone was assessed by pressure myography. Gene expression was measured by quantitative PCR. Results: Oxygen exposure was associated with increased 8-iso-prostaglandin (PG)F2α in newborn mouse lungs. Both 8-iso-PGE2 and 8-iso-PGF2α induced concentration-dependent constriction of the isolated term DA, which was reversed by the thromboxane A2 (TxA2) receptor antagonist SQ29548. SQ29548 pretreatment unmasked an isoprostane-induced DA dilation mediated by the EP4 PG receptor. Exposure of the preterm DA to 8-iso-PGE2 caused unexpected DA relaxation that was reversed by EP4 antagonism. In contrast, exposure to 8-iso-PGF2α caused preterm DA constriction via TxA2 receptor activation. Further investigation revealed the predominance of the TxA2 receptor at term, whereas the EP4 receptor was expressed and functionally active from mid-gestation onward. Conclusion: This study identifies a novel physiological role for isoprostanes during postnatal vascular transition and provide evidence that oxidative stress may act on membrane lipids to produce vasoactive mediators that stimulate physiological DA closure at birth or induce pathological patency of the preterm DA.",
author = "Chen, {Jian Xiong} and O'Mara, {Patrick W.} and Poole, {Stanley D.} and Naoko Brown and Ehinger, {Noah J.} and Slaughter, {James C.} and Paria, {Bibhash C.} and Aschner, {Judy L.} and Jeff Reese",
year = "2012",
month = "8",
doi = "10.1038/pr.2012.58",
language = "English (US)",
volume = "72",
pages = "122--128",
journal = "Pediatric Research",
issn = "0031-3998",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

TY - JOUR

T1 - Isoprostanes as physiological mediators of transition to newborn life

T2 - Novel mechanisms regulating patency of the term and preterm ductus arteriosus

AU - Chen, Jian Xiong

AU - O'Mara, Patrick W.

AU - Poole, Stanley D.

AU - Brown, Naoko

AU - Ehinger, Noah J.

AU - Slaughter, James C.

AU - Paria, Bibhash C.

AU - Aschner, Judy L.

AU - Reese, Jeff

PY - 2012/8

Y1 - 2012/8

N2 - Background: Increased oxygen tension at birth regulates physiologic events that are essential to postnatal survival, but the accompanying oxidative stress may also generate isoprostanes. We hypothesized that isoprostanes regulate ductus arteriosus (DA) function during postnatal vascular transition. Methods: Isoprostanes were measured by gas chromatography-mass spectrometry. DA tone was assessed by pressure myography. Gene expression was measured by quantitative PCR. Results: Oxygen exposure was associated with increased 8-iso-prostaglandin (PG)F2α in newborn mouse lungs. Both 8-iso-PGE2 and 8-iso-PGF2α induced concentration-dependent constriction of the isolated term DA, which was reversed by the thromboxane A2 (TxA2) receptor antagonist SQ29548. SQ29548 pretreatment unmasked an isoprostane-induced DA dilation mediated by the EP4 PG receptor. Exposure of the preterm DA to 8-iso-PGE2 caused unexpected DA relaxation that was reversed by EP4 antagonism. In contrast, exposure to 8-iso-PGF2α caused preterm DA constriction via TxA2 receptor activation. Further investigation revealed the predominance of the TxA2 receptor at term, whereas the EP4 receptor was expressed and functionally active from mid-gestation onward. Conclusion: This study identifies a novel physiological role for isoprostanes during postnatal vascular transition and provide evidence that oxidative stress may act on membrane lipids to produce vasoactive mediators that stimulate physiological DA closure at birth or induce pathological patency of the preterm DA.

AB - Background: Increased oxygen tension at birth regulates physiologic events that are essential to postnatal survival, but the accompanying oxidative stress may also generate isoprostanes. We hypothesized that isoprostanes regulate ductus arteriosus (DA) function during postnatal vascular transition. Methods: Isoprostanes were measured by gas chromatography-mass spectrometry. DA tone was assessed by pressure myography. Gene expression was measured by quantitative PCR. Results: Oxygen exposure was associated with increased 8-iso-prostaglandin (PG)F2α in newborn mouse lungs. Both 8-iso-PGE2 and 8-iso-PGF2α induced concentration-dependent constriction of the isolated term DA, which was reversed by the thromboxane A2 (TxA2) receptor antagonist SQ29548. SQ29548 pretreatment unmasked an isoprostane-induced DA dilation mediated by the EP4 PG receptor. Exposure of the preterm DA to 8-iso-PGE2 caused unexpected DA relaxation that was reversed by EP4 antagonism. In contrast, exposure to 8-iso-PGF2α caused preterm DA constriction via TxA2 receptor activation. Further investigation revealed the predominance of the TxA2 receptor at term, whereas the EP4 receptor was expressed and functionally active from mid-gestation onward. Conclusion: This study identifies a novel physiological role for isoprostanes during postnatal vascular transition and provide evidence that oxidative stress may act on membrane lipids to produce vasoactive mediators that stimulate physiological DA closure at birth or induce pathological patency of the preterm DA.

UR - http://www.scopus.com/inward/record.url?scp=84864329644&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84864329644&partnerID=8YFLogxK

U2 - 10.1038/pr.2012.58

DO - 10.1038/pr.2012.58

M3 - Article

C2 - 22565502

AN - SCOPUS:84864329644

VL - 72

SP - 122

EP - 128

JO - Pediatric Research

JF - Pediatric Research

SN - 0031-3998

IS - 2

ER -