Journal Article

Type 2 diabetes severely impairs structural and functional adaptation of rat resistance arteries to chronic changes in blood flow

Eric J. Belin de Chantemèle, Emilie Vessières, Anne-Laure Guihot, Bertrand Toutain, Maud Maquignau, Laurent Loufrani and Daniel Henrion

in Cardiovascular Research

Published on behalf of European Society of Cardiology

Volume 81, issue 4, pages 788-796
Published in print March 2009 | ISSN: 0008-6363
Published online December 2008 | e-ISSN: 1755-3245 | DOI: http://dx.doi.org/10.1093/cvr/cvn334
Type 2 diabetes severely impairs structural and functional adaptation of rat resistance arteries to chronic changes in blood flow

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Aims

Endothelial dysfunction in resistance arteries (RAs) leads to end-organ damage in type 2 diabetes. Remodelling of RAs in response to chronic increases in blood flow depends on the integrity of the endothelium. Since type 2 diabetes impairs endothelial sensitivity to flow and increases oxidative stress, we hypothesized that flow-induced remodelling in RAs would be impaired in diabetes. Thus, we studied the structural and functional adaptation of RAs from Zucker diabetic fatty (ZDF) and lean Zucker (LZ) rats to chronic changes in flow.

Methods and results

Mesenteric RAs were alternatively ligated so that one artery was submitted to high flow (HF) and compared with normal-flow (NF) arteries located at distance. After 3 weeks, arteries were studied in vitro (n = 10 rats per group). Arterial diameter (468 vs. 394 ± 8 µm) and endothelial (acetylcholine)-dependent dilation (91 ± 8 vs. 75 ± 6% dilation) were higher in HF than in NF arteries in LZ rats. In ZDF rats, diameter (396 ± 9 vs. 440 ± 17 µm) and acetylcholine-mediated dilation (42 ± 8 vs. 75 ± 7%) were lower in HF than in NF arteries. Nevertheless, endothelial NO synthase and NADP(H) oxidase subunits (gp91, p67) expression level and superoxide production (dihydroethidium staining) were higher in HF than in NF arteries in both strains, suggesting an efficient flow-sensing process in ZDF rats. In ZDF rats, basal oxidative stress was higher compared with LZ rats: dihydroethidium staining was higher in NF and HF arteries from ZDF rats, and acetylcholine-mediated dilation was improved by an acute antioxidant (tempol) in NF and HF arteries from ZDF rats. Thus, superoxide overproduction in ZDF rats impaired NO-dependent dilation and HF remodelling. Indeed, a chronic treatment with tempol increased HF artery diameter and endothelium-dependent dilation in ZDF rats.

Conclusion

In type 2 diabetic rats, a chronic increase in blood flow failed to induce outward remodelling and to improve endothelium-dependent dilation, mainly because of superoxide overproduction.

Keywords: Blood flow; Shear stress; Resistance arteries; Type 2 diabetes; Zucker diabetic fatty rats; Endothelium; Nitric oxide; Reactive oxygen species

Journal Article.  5609 words.  Illustrated.

Subjects: Cardiovascular Medicine

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