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

E. J. Young, M. A. Hill, W. B. Wiehler, Christopher Triggle, J. J. Reid

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)872-881
Number of pages10
JournalDiabetologia
Volume51
Issue number5
DOIs
Publication statusPublished - May 2008
Externally publishedYes

Fingerprint

Zucker Rats
Connexins
Mesenteric Arteries
Endothelium
Insulin
Acetylcholine
Messenger RNA
Connexin 43
Gap Junctions
Myography
Cromakalim
Charybdotoxin
Apamin
Video Microscopy
Proteins
Blood Vessels
Insulin Resistance
Real-Time Polymerase Chain Reaction
Nitric Oxide
Western Blotting

Keywords

  • Connexins
  • Diabetes
  • EDHF
  • Endothelium-derived hyperpolarising factor
  • Gap junctions
  • Insulin resistance
  • Mesenteric artery

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine

Cite this

Reduced EDHF responses and connexin activity in mesenteric arteries from the insulin-resistant obese Zucker rat. / Young, E. J.; Hill, M. A.; Wiehler, W. B.; Triggle, Christopher; Reid, J. J.

In: Diabetologia, Vol. 51, No. 5, 05.2008, p. 872-881.

Research output: Contribution to journalArticle

Young, E. J. ; Hill, M. A. ; Wiehler, W. B. ; Triggle, Christopher ; Reid, J. J. / Reduced EDHF responses and connexin activity in mesenteric arteries from the insulin-resistant obese Zucker rat. In: Diabetologia. 2008 ; Vol. 51, No. 5. pp. 872-881.
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AU - Hill, M. A.

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AU - Triggle, Christopher

AU - Reid, J. J.

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