Evidence map›Paper›PMID 20590639›Full record

ArticleBritish journal of pharmacology2010

Openers of small conductance calcium-activated potassium channels selectively enhance NO-mediated bradykinin vasodilatation in porcine retinal arterioles.

T Dalsgaard, C Kroigaard, M Misfeldt, T Bek, U Simonsen

Open access · greenAbstract read
In one paragraph

Article in British journal of pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
3.4field-weighted citation impact, top 7% 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

25 citing papers in PubMed, 47 citations in OpenAlex.

  1. Kinin BInflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024
    Article
  2. CaInternational journal of molecular sciences · 2023
    Review
  3. Article
  4. Article
  5. Article
  6. Vasodilatory Effect ofMolecules (Basel, Switzerland) · 2020
    Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Role of in vivo vascular redox in resistance arteries.Hypertension (Dallas, Tex. : 1979) · 2015
    Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Article
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

5 authors at 2 institutions in 1 country.

T DalsgaardDepartment of Pharmacology, Aarhus University, Aarhus C, Denmark. thomas.dalsgaard@farm.au.dk
C Kroigaard
M Misfeldt
T Bek
U Simonsen
Aarhus University · DKAarhus University Hospital · DK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

background and purposeSmall (SK(Ca) or K(Ca)2) and intermediate (IK(Ca) or K(Ca)3.1) conductance calcium-activated potassium channels are involved in regulation of vascular tone and blood pressure. The present study investigated whether NS309 (6,7-dichloro-1H-indole-2,3-dione 3-oxime) and CyPPA (cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine), which are selective openers of SK(Ca) and IK(Ca) channels and of SK(Ca)2 and SK(Ca)3 channels, respectively, enhance endothelium-dependent vasodilatation in porcine retinal arterioles. EXPERIMENTAL APPROACH: In porcine retinal arterioles, SK(Ca)3 and IK(Ca) protein localization was examined by immunolabelling. Endothelial cell calcium was measured by fluorescence imaging. For functional studies, arterioles with internal diameters of 116 +/- 2 microm (n = 276) were mounted in microvascular myographs for isometric tension recordings. KEY

resultsSK(Ca)3 and IK(Ca) protein was localized in the endothelium. Bradykinin, but not NS309 or CyPPA increased endothelial cell calcium. Pre-incubation with NS309 or CyPPA enhanced bradykinin relaxation without changing endothelial cell calcium. This enhanced relaxation was abolished by blocking SK(Ca) channels with apamin. In the presence of NS309 or CyPPA, mainly inhibition of NO synthase with asymmetric dimethylarginine, but also inhibition of cyclooxygenase with indomethacin, reduced bradykinin relaxation. Bradykinin relaxation was completely abolished by NO synthase and cyclooxygenase inhibition together with a NO scavenger, oxyhaemoglobin. CONCLUSIONS AND IMPLICATIONS: In porcine retinal arterioles, bradykinin increases endothelial cell calcium leading to activation of SK(Ca) and IK(Ca) channels. Without altering endothelial cell calcium, NS309 and CyPPA open SK(Ca) channels that enhance NO-mediated bradykinin relaxations. These results imply that opening SK(Ca) channels improves endothelium-dependent relaxation and makes this channel a potential target for treatments aimed at restoring retinal blood flow.

Indexed as

AnimalsApaminArteriolesBradykininCalciumEndothelium, VascularIndolesIntermediate-Conductance Calcium-Activated Potassium ChannelsNitric OxideNitric Oxide SynthaseOximesPyrazolesPyrimidinesRetinal ArterySmall-Conductance Calcium-Activated Potassium ChannelsSwine6,7-dichloro-1H-indole-2,3-dione 3-oximeApaminBradykininCalciumcyclohexyl-(2-(3,5-dimethylpyrazol-1-yl)-6-methylpyrimidin-4-yl)amineIndolesIntermediate-Conductance Calcium-Activated Potassium ChannelsNitric OxideNitric Oxide SynthaseOximesPyrazolesPyrimidinesSmall-Conductance Calcium-Activated Potassium Channels

Identifiers

PMID20590639
PMCPMC2938820
OpenAlexW1799090833

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.