Evidence map›Paper›PMID 18660830›Full record

ArticleBritish journal of pharmacology2008

Superoxide from NADPH oxidase upregulates type 5 phosphodiesterase in human vascular smooth muscle cells: inhibition with iloprost and NONOate.

S Muzaffar, N Shukla, M Bond, G B Sala-Newby, A C Newby, G D Angelini, J Y Jeremy

Expression of concernOpen access · greenAbstract read
In one paragraph

Article in British journal of pharmacology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It carries an expression of concern. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
3.1field-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.

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

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors at 2 institutions in 1 country.

S MuzaffarBristol Heart Institute, University of Bristol, Bristol, UK. s.muzaffar@bristol.ac.uk
N Shukla
M Bond
G B Sala-Newby
A C Newby
G D Angelini
J Y Jeremy
NIHR Bristol Cardiovascular Biomedical Research Unit · GBUniversity of Bristol · GB

Funding

British Heart Foundation SS/06/056/20884
6 · The paper itself

Abstract

background and purposeTo determine whether there is an association between vascular NADPH oxidase (NOX), superoxide, the small GTPase Rac(1) and PDE type 5 (PDE5) in human vascular smooth muscle cell (hVSMCs). EXPERIMENTAL APPROACH: hVSMCs were incubated with xanthine-xanthine oxidase (X-XO; a superoxide generating system) or the thromboxane A(2) analogue, U46619 (+/-superoxide dismutase (SOD) or apocynin) for 16 h. The expression of PDE5 and NOX-1 was assessed using Western blotting and superoxide measured. The role of Rac(1) in superoxide generation was assessed by overexpressing either the dominant-negative or constitutively active Rac isoforms. The effects of iloprost, DETA-NONOate and the Rho-kinase inhibitor, Y27632, on PDE5 and NOX-1 expression were also studied. KEY

resultsFollowing 16 h incubation, U46619 and X-XO promoted the expression of PDE5 and NOX-1, an effect blocked by SOD or apocynin when co-incubated over the same time course. X-XO and U46619 both promoted the formation of superoxide. Overexpression of dominant-negative Rac(1) or addition of iloprost, DETA-NONOate or Y27632 completely blocked both superoxide release and PDE5 protein expression and activity. CONCLUSIONS AND IMPLICATIONS: These data demonstrate that superoxide derived from NOX upregulates the expression of PDE5 in human VSMCs. As PDE5 hydrolyses cyclic GMP, this effect may blunt the vasculoprotective actions of NO.

Indexed as

Muscle, Smooth, VascularPhosphodiesterase 5 InhibitorsCells, CulturedCyclic Nucleotide Phosphodiesterases, Type 5HumansIloprostNADPH OxidasesNitric Oxide DonorsNitroso CompoundsSaphenous VeinSuperoxidesUp-RegulationVasodilator Agents2,2'-(hydroxynitrosohydrazono)bis-ethanamineCyclic Nucleotide Phosphodiesterases, Type 5IloprostNADPH OxidasesNitric Oxide DonorsNitroso CompoundsPhosphodiesterase 5 InhibitorsSuperoxidesVasodilator Agents

Identifiers

PMID18660830
PMCPMC2597240
OpenAlexW2057711911

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.