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Type 2 diabetes severely impairs structural and functional adaptation of rat resistance arteries to chronic changes in blood flow: Diabetes impairs flow-mediated remodeling

Abstract : Endothelial dysfunction in resistance arteries leads to end organ damages in type 2 diabetes. The capacity of the microcirculation to adapt or remodel in response to changes in blood flow or shear stress is essential for an optimal organ perfusion. Chronic increases in blood flow enhance arterial diameter and endothelium-dependent dilation.Since type 2 diabetes impairs endothelial sensitivity to flow (shear stress) and increases oxidative stress, we hypothesized that Zucker diabetic fatty rats (ZDF) would present an impaired flow-induced remodeling in resistance artery. Aim: The goal of the study was to compare the structural and functional adaptations of mesenteric arteries from lean (LZ) and ZDF rats, to chronic changes in blood flow. Methods: Two mesenteric resistance arteries were ligated in order to increase blood flow in a third artery. This artery was thus submitted, in vivo, to high flow (HF) and compared to normal flow (NF) arteries located at distance. After 3 weeks arteries were studied in vitro (n= 10 rats per group).Results: Arterial diameter (468 vs 394±8µm) 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, arterial diameter (396±9 vs 440±17µm) and acetylcholine-mediated dilation (42±8 vs 75±7% dilation) were lower in HF than in NF arteries. Nevertheless, endothelial NO-synthase and NADP(H)-oxidase subunits (gp91, p67) expression level and superoxide production were higher in HF than in NF arteries in both LZ and ZDF rats HF suggesting an efficient flow-sensing process in both ZDF and LZ rats. But, in ZDF rats basal oxidative stress was higher compared to LZ rats: a) dihydroethydium staining was higher in both NF and HF arteries in ZDF than in LZ rats and b) acetylcholine-mediated dilation was improved by an acute antioxidant (tempol) in NF and HF arteries from ZDF rats (no effect in LZ rats NF arteries). As a consequence, oxidative stress, slightly increased in LZ rats HF arteries was strongly increased in ZDF rats HF vessels. This led to an excessive superoxide production impairing NO-dependent dilation and HF-remodeling. Finally, a chronic treatment with tempol restored HF arteries diameter (426±13 in NF vs 471±16µm in HF arteries) and endothelium-dependent dilation in ZDF rats. Conclusion: In type 2 diabetic rats increasing blood flow chronically failed to induce outward remodeling and to improve endothelium-dependent dilation; mainly because of superoxide overproduction.
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Submitted on : Sunday, December 7, 2008 - 10:29:11 AM
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Eric Belin de Chantemèle, Emilie Vessières, Anne-Laure Guihot, Bertrand Toutain, Maud Maquignau, et al.. Type 2 diabetes severely impairs structural and functional adaptation of rat resistance arteries to chronic changes in blood flow: Diabetes impairs flow-mediated remodeling. Cardiovascular Research, Oxford University Press (OUP), 2008, pp.000. ⟨10.1093/cvr/cvn338⟩. ⟨inserm-00344939⟩

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