Evidence map›Paper›PMID 9927704›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America1999

Isometric contraction induces the Ca2+-independent activation of the endothelial nitric oxide synthase.

I Fleming, J Bauersachs, A Schäfer, D Scholz, J Aldershvile, R Busse

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
5.5field-weighted citation impact, top 3% 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

26 citing papers in PubMed, 114 citations in OpenAlex.

  1. Trial
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  7. Stimulation history affects vasomotor responses in rat mesenteric arterioles.Pflugers Archiv : European journal of physiology · 2019
    Article
  8. Article
  9. Inwardly rectifying KThe Journal of physiology · 2017
    Article
  10. Article
  11. Exercise training improves vascular mitochondrial function.American journal of physiology. Heart and circulatory physiology · 2016
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  14. Review
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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 2 institutions in 2 countries.

I FlemingInstitut für Kardiovaskuläre Physiologie, Klinikum der J. W. Goethe-Universität, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany. fleming@em.uni-frankfurt.de
J Bauersachs
A Schäfer
D Scholz
J Aldershvile
R Busse
University of Copenhagen · DKOrthopaedic University Hospital Friedrichsheim · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Shear stress and tyrosine phosphatase inhibitors have been shown to activate the endothelial NO synthase (eNOS) in a Ca2+/calmodulin-independent manner. We report here that isometric contraction of rabbit aorta activates eNOS by a pharmacologically identical pathway. Endothelium-intact aortic rings were precontracted under isometric conditions up to 60% of the maximal phenylephrine-induced tone. The NO synthase inhibitor NGnitro-L-arginine (L-NA) and the soluble guanylyl cyclase inhibitor NS 2028 induced an additional contraction, the amplitude of which depended on the level of precontraction. The maximal production of NO by isometrically contracted aortic rings (as estimated by the increase in cGMP in detector smooth muscle cells in a superfusion bioassay) was observed during the initial phase of isometric contraction and was greater than that detected following the application of acetylcholine. The supplementary L-NA-induced increase in vascular tone was inhibited by the nonselective kinase inhibitor staurosporine and the tyrosine kinase inhibitors erbstatin A and herbimycin A. Another tyrosine kinase inhibitor, genistein, the calmodulin antagonist calmidazolium, and the selective protein kinase C inhibitor, Ro 31-8220, had no effect. Coincident with the enhanced NO formation during isometric contraction was an increase in the tyrosine phosphorylation of endothelial proteins, which also correlated with the level of precontraction. Thus, isometric contraction activates eNOS via a Ca2+-independent, tyrosine kinase inhibitor-sensitive pathway and, like shear stress, seems to be an independent determinant of mechanically induced NO formation.

Indexed as

1-Methyl-3-isobutylxanthineAcetylcholineAnimalsAorta, ThoracicBenzoquinonesCalciumCalmodulinCells, CulturedCyclic GMPEndothelium, VascularEnzyme ActivationEnzyme InhibitorsFemaleGenisteinHydroquinonesImidazoles1-Methyl-3-isobutylxanthineAcetylcholineBenzoquinonesCalciumcalmidazoliumCalmodulinCyclic GMPEnzyme InhibitorserbstatinGenisteinherbimycinHydroquinonesImidazolesIndolesLactams, MacrocyclicNitric Oxide SynthaseNitric Oxide Synthase Type IIINitroarginineNS 2028OxadiazolesOxazinesQuinonesRifabutinRo 31-8220Staurosporine

Identifiers

PMID9927704
PMCPMC15361
OpenAlexW2049860005

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.