Evidence map›Paper›PMID 21671887›Full record

ArticleClinical science (London, England : 1979)2011

Acute simvastatin increases endothelial nitric oxide synthase phosphorylation via AMP-activated protein kinase and reduces contractility of isolated rat mesenteric resistance arteries.

Luciana V Rossoni, Mark Wareing, Camilla F Wenceslau, Mahmood Al-Abri, Chris Cobb, Clare Austin

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical science (London, England : 1979), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
3.6field-weighted citation impact, top 6% 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

28 citing papers in PubMed, 66 citations in OpenAlex.

  1. Article
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  12. BRG1 ActivatesFrontiers in cell and developmental biology · 2020
    Article
  13. Review
  14. Article
  15. Article
  16. Article
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  19. Article
  20. Novel therapeutic strategies for adult obese asthmatics.Immunology and allergy clinics of North America · 2014
    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

6 authors at 1 institution in 1 country.

Luciana V RossoniDepartment of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Mark Wareing
Camilla F Wenceslau
Mahmood Al-Abri
Chris Cobb
Clare Austin
Universidade de São Paulo · BR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Statins can have beneficial cholesterol-independent effects on vascular contractility, which may involve increases in the bioavailability of NO (nitric oxide) as a result of phosphorylation of eNOS (endothelial NO synthase). Although this has been attributed to phosphorylation of Akt (also known as protein kinase B), studies in cultured cells have shown that statins can phosphorylate AMPK (AMP-activated protein kinase); it is unknown whether this has functional effects in intact arteries. Thus we investigated the acute effects of simvastatin on resistance arterial contractile function, evaluating the involvement of NO, Akt and AMPK. Isolated rat mesenteric resistance arteries were mounted on a wire myograph. The effects of incubation (1 and 2 h) with simvastatin (0.1 or 1 μM) on contractile responses were examined in the presence and absence of L-NNA (N-nitro-L-arginine; 10 μM) or mevalonate (1 mM). Effects on eNOS, phospho-eNOS (Ser1177), and total and phospho-Akt and -AMPK protein expression were investigated using Western blotting. The effect of AMPK inhibition (compound C, 10 μM) on eNOS phosphorylation and contractile responses were also studied. Simvastatin (1 μM, 2 h) significantly reduced constriction to U46619 and phenylephrine and enhanced dilations to ACh (acetylcholine) in depolarized, but not in U46619-pre-constricted arteries. These effects were completely and partially prevented by L-NNA and mevalonate respectively. Simvastatin increased eNOS and AMPKα phosphorylation, but had no effect on Akt protein expression and phosphorylation after 2 h incubation. Compound C prevented the effects of simvastatin on eNOS phosphorylation and contractility. Thus simvastain can acutely modulate resistance arterial contractile function via mechanisms that involve the AMPK/phospho-eNOS (Ser1177)/NO-dependent pathway.

Indexed as

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic AcidAMP-Activated Protein KinasesAnimalsDose-Response Relationship, DrugHydroxymethylglutaryl-CoA Reductase InhibitorsMaleMesenteric ArteriesNitric OxideNitric Oxide Synthase Type IIIPhosphorylationProto-Oncogene Proteins c-aktRatsRats, WistarSimvastatinTissue Culture TechniquesVasoconstriction15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic AcidAMP-Activated Protein KinasesHydroxymethylglutaryl-CoA Reductase InhibitorsNitric OxideNitric Oxide Synthase Type IIINos3 protein, ratProto-Oncogene Proteins c-aktSimvastatinVasoconstrictor Agents

Identifiers

PMID21671887
PMCPMC3174052
OpenAlexW2131894979

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.