Endothelial dysfunction in the streptozotocin-induced diabetic apoE-deficient mouse Academic Article uri icon

Overview

MeSH Major

  • Diabetes Mellitus, Experimental
  • Endothelium, Vascular

abstract

  • Endothelial dysfunction plays a role in the development of atherosclerosis and diabetes-associated vascular disease and, in the streptozotocin (STZ)-induced apoE-deficient diabetic mouse, we report that, when compared to the citrate (CIT)-treated nondiabetic apoE-deficient control, acetylcholine (Ach)-mediated endothelium-dependent relaxation was reduced in the small mesenteric arteries (SMA) and the plaque-prone regions of the aorta from the STZ-diabetic mouse. In the SMA the component of Ach-mediated relaxation that was attributed to nitric oxide (NO) from STZ-treated diabetic apoE-deficient mice was enhanced; however, the endothelium-derived hyperpolarizing factor (EDHF)-mediated component was reduced. The EDHF component was assessed by determining the component of the Ach-mediated response that was resistant to the combination of the NO synthase (NOS) inhibitor Nomega-nitro-L-arginine methyl ester, cyclooxygenase inhibitor, indomethacin, and soluble guanylate cyclase inhibitor, ODQ, and inhibited by the combination of the intermediate conductance KCa (IKCa) inhibitor TRAM-34 and the small-conductance KCa (SKCa) inhibitor apamin. Endothelial NOS was increased but SK2, SK3 and connexin (Cx) 37 mRNA expressions were significantly (P<0.05) decreased in the SMA from STZ-treated apoE-deficient mice compared to the CIT-treated controls. There was no difference in the IKCa expression or in Cx 40, 43 and 45 mRNA levels between STZ- and CIT-treated mice. The microvasculature of STZ-induced apoE-deficient mice developed endothelial dysfunction, which may be linked to a decrease in the contribution of the EDHF component due to a decrease in SK2 and 3 and Cx 37 expression.

publication date

  • December 2005

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC1751246

Digital Object Identifier (DOI)

  • 10.1038/sj.bjp.0706417

PubMed ID

  • 16231005

Additional Document Info

start page

  • 1110

end page

  • 8

volume

  • 146

number

  • 8