Evidence map›Paper›PMID 21351102›Full record

ArticleJournal of cellular physiology2011

Attenuated vasodilatation in lambs with endogenous and exogenous activation of cGMP signaling: role of protein kinase G nitration.

Saurabh Aggarwal, Christine M Gross, Sanjiv Kumar, Sanjeev Datar, Peter Oishi, Gokhan Kalkan, Christian Schreiber, Sohrab Fratz, Jeffrey R Fineman, Stephen M Black

Registry-linked trialOpen access · greenAbstract read
In one paragraph

Article in Journal of cellular physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01825369 (Phase 1 Study of the Safety and Pharmacokinetics of Perioperative IV L-carnitine Administration in Patients With Congenital Heart Disease With Increased Pulmonary Blood Flow), which is not on this map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
2.9field-weighted citation impact, top 9% 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.

NCT01825369 phase1withdrawnnot on this mapstarted 2014, after this paper: background citation

Phase 1 Study of the Safety and Pharmacokinetics of Perioperative IV L-carnitine Administration in Patients With Congenital Heart Disease With Increased Pulmonary Blood Flow

TypeinterventionalSponsorUniversity of California, San FranciscoRan2014 to 2020Enrolled0ConditionsHeart Septal Defects, Ventricular, Atrioventricular Septal DefectArmsIV L-carnitine
3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 35 citations in OpenAlex.

  1. Right ventricle remodelling: fromJournal of molecular and cellular cardiology plus · 2025
    Review
  2. Article
  3. Article
  4. Article
  5. Animal models of right heart failure.Cardiovascular diagnosis and therapy · 2020
    Review
  6. Review
  7. Review
  8. Endothelial and Smooth Muscle Cell Interactions in the Pathobiology of Pulmonary Hypertension.American journal of respiratory cell and molecular biology · 2016
    Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. The NO/ONOO-cycle as the central cause of heart failure.International journal of molecular sciences · 2013
    Review
  15. Review
  16. Article
  17. Article
  18. Review
  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

10 authors at 4 institutions in 2 countries.

Saurabh AggarwalPulmonary Disease Program, Vascular Biology Center, Georgia Health Sciences University, Augusta, Georgia 30912, USA.
Christine M Gross
Sanjiv Kumar
Sanjeev Datar
Peter Oishi
Gokhan Kalkan
Christian Schreiber
Sohrab Fratz
Jeffrey R Fineman
Stephen M Black
Augusta University Health · USUniversity of California, San Francisco · USDeutsches Herzzentrum München · DELudwig-Maximilians-Universität München · DE

Funding

Pediatric Critical Care Scientist Development ProgramK12HD047349 · NICHD · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI HEATHER T. KEENAN, Kevin M Watt · 2004 to 2026
$17.0M
PERINATAL PULMONARY HYPERTENSION: DEVELOPMENT MEDIATORSR01HL061284 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FINEMAN, JEFFREY R · 1999 to 2016
$8.3M
PERINATAL REGULATION OF THE ENDOTHELIAL NOS GENER01HL060190 · NHLBI · UNIVERSITY OF MONTANA · PI Stephen M Black · 1998 to 2026
$7.1M
Research Training in Pediatric Critical Care MedicineT32HD049303 · NICHD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JEFFREY R FINEMAN · 2006 to 2026
$3.1M
ROS in Pulmonary Hypertension: Role of ADMAR01HL067841 · NHLBI · UNIVERSITY OF MONTANA · PI BLACK, STEPHEN M · 2002 to 2011
$2.6M
Perinatal regulation of TGF-beta1 during vascular remodelingR01HL084739 · NHLBI · AUGUSTA UNIVERSITY · PI BLACK, STEPHEN M · 2007 to 2010
$1.5M
Role of altered carnitine metabolism in perinatal endothelial dysfunctionR21HD057406 · NICHD · AUGUSTA UNIVERSITY · PI BLACK, STEPHEN M · 2008 to 2009
$423k
NHLBI NIH HHS HL084739NHLBI NIH HHS HL60190NHLBI NIH HHS HL61284NHLBI NIH HHS HL67841NHLBI NIH HHS R01 HL060190NHLBI NIH HHS R01 HL061284NHLBI NIH HHS R01 HL067841NHLBI NIH HHS R01 HL084739NICHD NIH HHS R21 HD057406NICHD NIH HHS R21HD057406NICHD NIH HHS T32 HD049303
6 · The paper itself

Abstract

Pulmonary vasodilation is mediated through the activation of protein kinase G (PKG) via a signaling pathway involving nitric oxide (NO), natriuretic peptides (NP), and cyclic guanosine monophosphate (cGMP). In pulmonary hypertension secondary to congenital heart disease, this pathway is endogenously activated by an early vascular upregulation of NO and increased myocardial B-type NP expression and release. In the treatment of pulmonary hypertension, this pathway is exogenously activated using inhaled NO or other pharmacological agents. Despite this activation of cGMP, vascular dysfunction is present, suggesting that NO-cGMP independent mechanisms are involved and were the focus of this study. Exposure of pulmonary artery endothelial or smooth muscle cells to the NO donor, Spermine NONOate (SpNONOate), increased peroxynitrite (ONOO(-) ) generation and PKG-1α nitration, while PKG-1α activity was decreased. These changes were prevented by superoxide dismutase (SOD) or manganese(III)tetrakis(1-methyl-4-pyridyl)porphyrin (MnTMPyP) and mimicked by the ONOO(-) donor, 3-morpholinosydnonimine N-ethylcarbamide (SIN-1). Peripheral lung extracts from 4-week old lambs with increased pulmonary blood flow and pulmonary hypertension (Shunt lambs with endogenous activation of cGMP) or juvenile lambs treated with inhaled NO for 24 h (with exogenous activation of cGMP) revealed increased ONOO(-) levels, elevated PKG-1α nitration, and decreased kinase activity without changes in PKG-1α protein levels. However, in Shunt lambs treated with L-arginine or lambs administered polyethylene glycol conjugated-SOD (PEG-SOD) during inhaled NO exposure, ONOO(-) and PKG-1α nitration were diminished and kinase activity was preserved. Together our data reveal that vascular dysfunction can occur, despite elevated levels of cGMP, due to PKG-1α nitration and subsequent attenuation of activity.

Indexed as

Second Messenger SystemsVasodilationAdministration, InhalationAnimalsAnimals, NewbornCells, CulturedCyclic GMPCyclic GMP-Dependent Protein KinasesCyclic GMP-Dependent Protein Kinase Type IDisease Models, AnimalEndothelial CellsEnzyme ActivationFree Radical ScavengersHypertension, PulmonaryMetalloporphyrinsMolsidomineCyclic GMPCyclic GMP-Dependent Protein KinasesCyclic GMP-Dependent Protein Kinase Type IFree Radical ScavengerslinsidomineMetalloporphyrinsMn(III) 5,10,15,20-tetrakis(N-methylpyridinium-2-yl)porphyrinMolsidomineNitric OxideNitric Oxide DonorsPeroxynitrous AcidPolyethylene Glycolspolyethylene glycol-superoxide dismutaseSperminespermine nitric oxide complexSuperoxide DismutaseVasodilator Agents

Identifiers

PMID21351102
PMCPMC3527072
OpenAlexW2023237713

What OpenQuestion holds

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Read underepoch 390

Registered trials

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.