Evidence map›Paper›PMID 22198908›Full record

ArticleAmerican journal of physiology. Lung cellular and molecular physiology2012

Apocynin improves oxygenation and increases eNOS in persistent pulmonary hypertension of the newborn.

Stephen Wedgwood, Satyan Lakshminrusimha, Kathryn N Farrow, Lyubov Czech, Sylvia F Gugino, Fernando Soares, James A Russell, Robin H Steinhorn

Abstract read
In one paragraph

Article in American journal of physiology. Lung cellular and molecular physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed, 1 pooled it
2.6field-weighted citation impact, top 11% 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

29 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Review
  6. Pulmonary hypertension and oxidative stress: Where is the link?Seminars in fetal & neonatal medicine · 2022
    Review
  7. Article
  8. Review
  9. Article
  10. Review
  11. Optimal oxygenation and role of free radicals in PPHN.Free radical biology & medicine · 2019
    Review
  12. Article
  13. Article
  14. Review
  15. Review
  16. Review
  17. Article
  18. Article
  19. Article
  20. 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

8 authors at 2 institutions in 1 country.

Stephen WedgwoodDeparment of Pediatrics, Northwestern University, Chicago, Illinois, USA. s-wedgwood@northwestern.edu
Satyan Lakshminrusimha
Kathryn N Farrow
Lyubov Czech
Sylvia F Gugino
Fernando Soares
James A Russell
Robin H Steinhorn
Northwestern University · USUniversity at Buffalo, State University of New York · US

Funding

REDOX REGULATION IN THE PERINATAL PULMONARY VASCULATURER01HL054705 · NHLBI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI STEINHORN, ROBIN H. · 2001 to 2013
$4.8M
Oxygen-Mediated Regulation of PDE5 in the Developing Pulmonary VasculatureK08HL086715 · NHLBI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI FARROW, KATHRYN N · 2007 to 2011
$647k
Antenatal Betamethasone in Late Preterm Gestation LambsR03HD060138 · NICHD · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI LAKSHMINRUSIMHA, SATYANARAYANA · 2009 to 2010
$159k
CGMP REGULATION IN THE DEVELOPING PULMONARY VASCULATURER29HL054705 · NHLBI · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI STEINHORN, ROBIN H · 1995 to 1998
–
NHLBI NIH HHS HL-54705NHLBI NIH HHS K08 HL-086715NHLBI NIH HHS K08 HL086715NHLBI NIH HHS R01 HL054705NICHD NIH HHS HD-060138
6 · The paper itself

Abstract

NADPH oxidase is a major source of superoxide anions in the pulmonary arteries (PA). We previously reported that intratracheal SOD improves oxygenation and restores endothelial nitric oxide (NO) synthase (eNOS) function in lambs with persistent pulmonary hypertension of the newborn (PPHN). In this study, we determined the effects of the NADPH oxidase inhibitor apocynin on oxygenation, reactive oxygen species (ROS) levels, and NO signaling in PPHN lambs. PPHN was induced in lambs by antenatal ligation of the ductus arteriosus 9 days prior to delivery. Lambs were treated with vehicle or apocynin (3 mg/kg intratracheally) at birth and then ventilated with 100% O(2) for 24 h. A significant improvement in oxygenation was observed in apocynin-treated lambs after 24 h of ventilation. Contractility of isolated fifth-generation PA to norepinephrine was attenuated in apocynin-treated lambs. PA constrictions to NO synthase (NOS) inhibition with N-nitro-l-arginine were blunted in PPHN lambs; apocynin restored contractility to N-nitro-l-arginine, suggesting increased NOS activity. Intratracheal apocynin also enhanced PA relaxations to the eNOS activator A-23187 and to the NO donor S-nitrosyl-N-acetyl-penicillamine. Apocynin decreased the interaction between NADPH oxidase subunits p22(phox) and p47(phox) and decreased the expression of Nox2 and p22(phox) in ventilated PPHN lungs. These findings were associated with decreased superoxide and 3-nitrotyrosine levels in the PA of apocynin-treated PPHN lambs. eNOS protein expression, endothelial NO levels, and tetrahydrobiopterin-to-dihydrobiopterin ratios were significantly increased in PA from apocynin-treated lambs, although cGMP levels did not significantly increase and phosphodiesterase-5 activity did not significantly decrease. NADPH oxidase inhibition with apocynin may improve oxygenation, in part, by attenuating ROS-mediated vasoconstriction and by increasing NOS activity.

Indexed as

AcetophenonesAnimalsAnimals, NewbornBiopterinsCyclic GMPCyclic Nucleotide Phosphodiesterases, Type 5Endothelium, VascularHypertension, PulmonaryLungNADPH OxidasesNitric OxideNitric Oxide DonorsNitric Oxide SynthaseNitric Oxide Synthase Type IIINorepinephrinePulmonary Artery3-nitrotyrosine7,8-dihydrobiopterinAcetophenonesacetovanilloneBiopterinsCyclic GMPCyclic Nucleotide Phosphodiesterases, Type 5NADPH OxidasesNitric OxideNitric Oxide DonorsNitric Oxide SynthaseNitric Oxide Synthase Type IIINorepinephrineReactive Oxygen SpeciessapropterinSuperoxidesTyrosine

Identifiers

PMID22198908
PMCPMC3311530
OpenAlexW2156158174

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.