RGD Reference Report - Imidazolineoxyl N-oxide prevents the impairment of vascular contraction caused by interleukin-1beta through several mechanisms. - Rat Genome Database

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Imidazolineoxyl N-oxide prevents the impairment of vascular contraction caused by interleukin-1beta through several mechanisms.

Authors: Soler, Marta  Camacho, Mercedes  Vila, Luís 
Citation: Soler M, etal., J Infect Dis. 2003 Sep 15;188(6):927-37. doi: 10.1086/377586. Epub 2003 Sep 4.
RGD ID: 401960074
Pubmed: PMID:12964126   (View Abstract at PubMed)
DOI: DOI:10.1086/377586   (Journal Full-text)

Overnight exposure to interleukin (IL)-1beta caused a dramatic hyporesponsiveness to phenylephrine, increased nitric oxide (NO) and prostacyclin production, and induced cycloxygenase-2 expression in rat aortic rings. Using different inhibitors, we found that this hyporeactivity was mediated by NO, prostacyclin, and activation of charybdotoxin-sensitive K(+) channels. The latter was independent of the presence of endothelium and NO and prostanoid synthesis during the challenge with phenylephrine. Activation of charybdotoxin-sensitive K(+) channels was probably due to NO stores formed during the exposition to IL-1beta; 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO), either when added with IL-1beta or in the organ bath, partially restored the contractility of IL-1beta-treated vessels. The cPTIO effect was mimicked by combinations of cyclooxygenase and NO-synthase inhibitors and by charybdotoxin. cPTIO significantly inhibited prostacyclin formation and prostacyclin-synthase activity during incubation with the cytokine. cPTIO antagonized the effect of IL-1beta by scavenging NO, reducing prostacyclin-synthase activity, and avoiding the contribution activation of K(+) channels.



Gene-Chemical Interaction Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PTGISHumancarboxy-PTIO decreases activityISOPtgis (Rattus norvegicus)cPTIO decreases activity of Ptgis protein in the aortaRGD 
PtgisRatcarboxy-PTIO decreases activityEXP cPTIO decreases activity of Ptgis protein in the aortaRGD 
PtgisMousecarboxy-PTIO decreases activityISOPtgis (Rattus norvegicus)cPTIO decreases activity of Ptgis protein in the aortaRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PtgisRatresponse to organic cyclic compound  IDA cPTIORGD 

Objects Annotated

Genes (Rattus norvegicus)
Ptgis  (prostaglandin I2 synthase)

Genes (Mus musculus)
Ptgis  (prostaglandin I2 (prostacyclin) synthase)

Genes (Homo sapiens)
PTGIS  (prostaglandin I2 synthase)


Additional Information