Evidence map›Paper›PMID 21890489›Full record

ReviewEuropean heart journal2012

Nitric oxide synthases: regulation and function.

Ulrich Förstermann, William C Sessa

2 registry-linked trialsOpen access · bronzeAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in European heart journal, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 2,042 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
2,042citing papers in PubMed, 4 pooled it
62.2field-weighted citation impact, top 1% 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.

NCT02894723 phase4unknown statusnot on this mapstarted 2016, after this paper: background citation

Efficacy of L-arginine Treatment on Blood Pressure Control Patients With Stage 1 Hypertension

TypeinterventionalSponsorMeir Medical CenterRan2016 to 2017Enrolled40ConditionsHypertensionArmsL-arginine, syrup
NCT04885153 nacompletednot on this mapstarted 2016, after this paper: background citation

Effects of Oral Fenofibrate on Retinal Thickness and Macular Volume: Assessments on Retinal Endothelial Vascular Dysfunction, Inflammation, and Angiogenesis in Diabetic Retinopathy With Dyslipidemia

TypeinterventionalSponsorIndonesia UniversityRan2016 to 2017Enrolled36ConditionsDiabetic Retinopathy, Dyslipidemias, Diabetes MellitusArmsFenofibrate, Placebo
3 · Its place in the literature

Who cites it

2,042 citing papers in PubMed, 4 syntheses or guidelines pooled it, 4,173 citations in OpenAlex.

  1. Pooled it
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  5. Trial
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  7. Review
  8. General View of Arachidonic Acid (AA) Metabolism.Reviews of physiology, biochemistry and pharmacology · 2027
    Review
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  14. Elemental analysis in menstrual effluent of women with PCOS: association with oxidative stress mechanisms: a case-control study.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026
    Article
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  16. Beyond the guidelines: Vascular function as the central determinant and therapeutic target in hypertension.Hypertension research : official journal of the Japanese Society of Hypertension · 2026
    Review
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1,982 more citing papers are in PubMed but not listed here.

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

2 authors at 2 institutions in 2 countries.

Ulrich FörstermannDepartment of Pharmacology, Johannes Gutenberg University Medical Center, 55101 Mainz, Germany. ulrich.forstermann@uni-mainz.de
William C Sessa
Johannes Gutenberg University Mainz · DEYale University · US

Funding

SOCS-1 and endothelial dysfunction in graft arteriosclerosisP01HL070295 · NHLBI · YALE UNIVERSITY · PI POBER, JORDAN S · 2001 to 2010
$17.9M
PHOSPHORYLATION AND ENDOTHELIAL NITRIC OXIDE PRODUCTIONR01HL064793 · NHLBI · YALE UNIVERSITY · PI SESSA, WILLIAM C · 2000 to 2016
$6.3M
Regulation of vascular remodeling &angiogenesis by NogoR01HL081190 · NHLBI · YALE UNIVERSITY · PI SESSA, WILLIAM C · 2005 to 2014
$4.1M
Endothelial NOS by Protein-Protein IntractionsR01HL061371 · NHLBI · YALE UNIVERSITY · PI SESSA, WILLIAM C · 1999 to 2008
$3.6M
microRNA regulation of endothelial functionsR01HL096670 · NHLBI · YALE UNIVERSITY · PI SESSA, WILLIAM C · 2010 to 2013
$1.8M
NHLBI NIH HHS P01 HL70295NHLBI NIH HHS R01 HL081190NHLBI NIH HHS R01 HL096670NHLBI NIH HHS R01 HL61371NHLBI NIH HHS R01 HL64793
6 · The paper itself

Abstract

Nitric oxide (NO), the smallest signalling molecule known, is produced by three isoforms of NO synthase (NOS; EC 1.14.13.39). They all utilize l-arginine and molecular oxygen as substrates and require the cofactors reduced nicotinamide-adenine-dinucleotide phosphate (NADPH), flavin adenine dinucleotide (FAD), flavin mononucleotide (FMN), and (6R-)5,6,7,8-tetrahydrobiopterin (BH(4)). All NOS bind calmodulin and contain haem. Neuronal NOS (nNOS, NOS I) is constitutively expressed in central and peripheral neurons and some other cell types. Its functions include synaptic plasticity in the central nervous system (CNS), central regulation of blood pressure, smooth muscle relaxation, and vasodilatation via peripheral nitrergic nerves. Nitrergic nerves are of particular importance in the relaxation of corpus cavernosum and penile erection. Phosphodiesterase 5 inhibitors (sildenafil, vardenafil, and tadalafil) require at least a residual nNOS activity for their action. Inducible NOS (NOS II) can be expressed in many cell types in response to lipopolysaccharide, cytokines, or other agents. Inducible NOS generates large amounts of NO that have cytostatic effects on parasitic target cells. Inducible NOS contributes to the pathophysiology of inflammatory diseases and septic shock. Endothelial NOS (eNOS, NOS III) is mostly expressed in endothelial cells. It keeps blood vessels dilated, controls blood pressure, and has numerous other vasoprotective and anti-atherosclerotic effects. Many cardiovascular risk factors lead to oxidative stress, eNOS uncoupling, and endothelial dysfunction in the vasculature. Pharmacologically, vascular oxidative stress can be reduced and eNOS functionality restored with renin- and angiotensin-converting enzyme-inhibitors, with angiotensin receptor blockers, and with statins.

Indexed as

AnimalsArginineBiopterinsCardiovascular AgentsCardiovascular DiseasesEndothelium, VascularGenetic TherapyHumansHydroxymethylglutaryl-CoA Reductase InhibitorsIsoenzymesMiceNeovascularization, PhysiologicNitric OxideNitric Oxide SynthaseNitric Oxide Synthase Type INitric Oxide Synthase Type IIArginineBiopterinsCardiovascular AgentsHydroxymethylglutaryl-CoA Reductase InhibitorsIsoenzymesNitric OxideNitric Oxide SynthaseNitric Oxide Synthase Type INitric Oxide Synthase Type IINitric Oxide Synthase Type IIIsapropterin

Identifiers

PMID21890489
PMCPMC3345541
OpenAlexW1997023449

What OpenQuestion holds

Texttitle and abstract
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.