Evidence map›Paper›PMID 25006423›Full record

ArticlePulmonary circulation2014

Hydrocortisone normalizes phosphodiesterase-5 activity in pulmonary artery smooth muscle cells from lambs with persistent pulmonary hypertension of the newborn.

Marta Perez, Stephen Wedgwood, Satyan Lakshminrusimha, Kathryn N Farrow, Robin H Steinhorn

Open access · bronzeAbstract read
In one paragraph

Article in Pulmonary circulation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.7field-weighted citation impact, top 16% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 25 citations in OpenAlex.

  1. Review
  2. Review
  3. Meconium aspiration syndrome: a comprehensive review.Journal of perinatology : official journal of the California Perinatal Association · 2023
    Review
  4. Article
  5. Pulmonary hypertension and oxidative stress: Where is the link?Seminars in fetal & neonatal medicine · 2022
    Review
  6. Review
  7. Review
  8. Optimal oxygenation and role of free radicals in PPHN.Free radical biology & medicine · 2019
    Review
  9. Review
  10. Article
  11. Review
  12. Persistent pulmonary hypertension of the newborn.Maternal health, neonatology and perinatology · 2015
    Article
  13. Article
  14. Article
  15. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 1 country.

Marta PerezDepartment of Pediatrics, Northwestern University, Chicago, Illinois, USA.
Stephen WedgwoodDepartment of Pediatrics, University of California Davis Medical Center, Sacramento, California, USA.
Satyan LakshminrusimhaDepartment of Pediatrics, University at Buffalo, Buffalo, New York, USA.
Kathryn N FarrowDepartment of Pediatrics, Northwestern University, Chicago, Illinois, USA.
Robin H SteinhornDepartment of Pediatrics, University of California Davis Medical Center, Sacramento, California, USA.
Northwestern University · USUniversity of California Davis Medical Center · USUniversity at Buffalo, State University of New York · US

Funding

Optimal Oxygenation in Neonatal Lung InjuryR01HD072929 · NICHD · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Satyanarayana Lakshminrusimha · 2012 to 2026
$5.4M
REDOX REGULATION IN THE PERINATAL PULMONARY VASCULATURER01HL054705 · NHLBI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI STEINHORN, ROBIN H. · 2001 to 2013
$4.8M
Redox Regulation of Vascular cGMP Signaling in Neonatal LungsR01HL109478 · NHLBI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI SCHUMACKER, PAUL T · 2011 to 2020
$4.2M
NHLBI NIH HHS R01 HL054705NHLBI NIH HHS R01 HL109478NICHD NIH HHS R01 HD072929
6 · The paper itself

Abstract

Phosphodiesterase-5 (PDE5) is the primary phosphodiesterase in the pulmonary vasculature. It degrades cyclic guanosine monophosphate (cGMP) and inhibits cGMP-mediated vasorelaxation. We previously reported that hydrocortisone treatment decreased hyperoxia-induced PDE5 activity and markers of oxidative stress in lambs with persistent pulmonary hypertension of the newborn (PPHN) ventilated with 100% O2. The objective of our study was to determine the molecular mechanism by which hydrocortisone downregulates PDE5 and oxidative stress in fetal pulmonary artery smooth muscle cells (FPASMCs) from PPHN lambs. PPHN FPASMC were incubated for 24 hours in either 21% or 95% O2. Some cells were treated with 100 nM hydrocortisone and/or ±1 μM helenalin, an inhibitor of nuclear factor κ B (NFκB), a redox-sensitive transcription factor. Exposure to hyperoxia led to increased PDE5 activity, oxidative stress, and NFκB activity. Pretreatment of PPHN FPASMC with hydrocortisone normalized PDE5 activity, decreased cytosolic oxidative stress, increased expression of extracellular superoxide dismutase and NFκB inhibitory protein, and decreased NFκB activity. Similarly, treatment with NFκB inhibitor, helenalin, decreased PDE5 activity. These data suggest that hyperoxia activates NFκB, which in turn induces PDE5 activity in PPHN FPASMC, whereas treatment with hydrocortisone attenuates these changes by blocking reactive oxygen species-induced NFκB activity.

Indexed as

hydrocortisoneNFκBoxidative stressPDE5PPHN

Identifiers

PMID25006423
PMCPMC4070767
OpenAlexW1967028956

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.