RGD Reference Report - Reduced EDHF responses and connexin activity in mesenteric arteries from the insulin-resistant obese Zucker rat. - Rat Genome Database

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Reduced EDHF responses and connexin activity in mesenteric arteries from the insulin-resistant obese Zucker rat.

Authors: Young, EJ  Hill, MA  Wiehler, WB  Triggle, CR  Reid, JJ 
Citation: Young EJ, etal., Diabetologia. 2008 May;51(5):872-81. doi: 10.1007/s00125-008-0934-y. Epub 2008 Mar 7.
RGD ID: 7207466
Pubmed: PMID:18324386   (View Abstract at PubMed)
DOI: DOI:10.1007/s00125-008-0934-y   (Journal Full-text)

AIMS/HYPOTHESIS: The objective of this study was to examine the effect of insulin resistance on endothelium-derived hyperpolarising factor (EDHF) and small mesenteric artery endothelial function using 25-week-old insulin-resistant obese Zucker rats (OZRs) and lean littermate control rats (LZRs). The involvement of gap junctions and their connexin subunits in the EDHF relaxation response was also assessed. METHODS: Mesenteric arteries were evaluated using the following assays: (1) endothelial function by pressure myography, with internal diameter recorded using video microscopy; (2) connexin protein levels by western blotting; and (3) Cx mRNA expression by real-time PCR. RESULTS: Relaxations in response to acetylcholine were significantly smaller in mesenteric arteries from the OZRs than the LZRs, whereas there was no difference in relaxations in response to levcromakalim. Responses to acetylcholine were not altered by nitric oxide inhibitors, but were abolished by charybdotoxin in combination with apamin, which blocked the EDHF component of the response. 40Gap27 significantly attenuated the response to acetylcholine in the LZRs, but had no effect in the OZRs. Connexin 40 protein and Cx40 mRNA levels in mesenteric vascular homogenates were significantly smaller in the OZRs than in the LZRs, with no difference in connexin 43 or Cx43 mRNA levels. CONCLUSIONS/INTERPRETATION: These findings demonstrate that endothelial dysfunction in mesenteric arteries from the insulin-resistant OZRs can be attributed to a defect in EDHF. The results also suggest that the defective EDHF is at least partly related to an impairment of connexin 40-associated gap junctions, through a decrease in connexin 40 protein and Cx40 mRNA expression in the OZRs.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
GJA5Humanobesity  ISOGja5 (Rattus norvegicus)mRNA and protein:decreased expression:mesenteric arteryRGD 
Gja5Ratobesity  IEP mRNA and protein:decreased expression:mesenteric arteryRGD 
Gja5Mouseobesity  ISOGja5 (Rattus norvegicus)mRNA and protein:decreased expression:mesenteric arteryRGD 

Objects Annotated

Genes (Rattus norvegicus)
Gja5  (gap junction protein, alpha 5)

Genes (Mus musculus)
Gja5  (gap junction protein, alpha 5)

Genes (Homo sapiens)
GJA5  (gap junction protein alpha 5)


Additional Information