Rosiglitazone reverses endothelial dysfunction but not remodeling of femoral artery in Zucker diabetic fatty rats

Cardiovascular Diabetology

Original Investigation

Xiaomei Guo¹  Xiao Lu¹  Ghassan S Kassab²  Karen M Zimmerman³  Jude E Onyia³  Sotirios K Karathanasis⁴  Richard G Peterson⁵ 

[1] Department of Biomedical Engineering, Indiana University Purdue University (IUPUI), 46202, Indianapolis, IN, USA;Department of Biomedical Engineering, Indiana University Purdue University (IUPUI), 46202, Indianapolis, IN, USA;Department of Cellular and Integrative Physiology, IUPUI, 46202, Indianapolis, IN, USA;Department of Surgery, IUPUI, 46202, Indianapolis, IN, USA;Indiana Center for Vascular Biology and Medicine, IUPUI, 46202, Indianapolis, IN, USA;Lilly and Company, 46204, Indianapolis, IN, USA;Lilly and Company, 46204, Indianapolis, IN, USA;AstraZeneca R&D, Molndal, Sweden;PreClinOmics, 46268, Indianapolis, IN, USA;

关键词: Endothelial Dysfunction;    Endothelial Function;    Rosiglitazone;    Vascular Remodel;    Superficial Femoral Artery;   

DOI  :  10.1186/1475-2840-9-19

 received in 2010-02-19, accepted in 2010-05-19,  发布年份 2010

来源: Springer

【 摘 要 】

ObjectivesEndothelial dysfunction precedes atherogenesis and clinical complications in type 2 diabetes. The vascular dysfunction in Zucker diabetic fatty (ZDF) rats was evaluated at different ages along with the effect of treatment with rosiglitazone (Rosi) on endothelial function and mechanical remodeling.MethodsThe Rosi treatment was given to ZDF rats for 3 weeks. The endothelium-dependent vasodilation and α-adrenoceptor-dependent vasoconstriction of femoral arteries were studied using an ex-vivo isovolumic myograph. The biomechanical passive property of the arteries was studied in Ca2+-free condition. The expressions of endothelial nitric oxide synthase (eNOS), α-adrenoceptor, matrix metalloproteinase 9 (MMP9), and elastase were evaluated.ResultsEndothelium-dependent vasorelaxation of the femoral artery was blunted at low doses in ZDF rats at 11 weeks of age and attenuated at all doses in ZDF rats at 19 weeks of age. The expression of eNOS was consistent with the endothelium-dependent vasorelaxation. The α-adrenoceptor was activated and the mechanical elastic modulus was increased in ZDF rats at 19 weeks of age. The expressions of α-adrenoceptor, MMP9, and elastase were up regulated in ZDF rats at 19 weeks of age. Rosi treatment for 3 weeks restored endothelium-dependent vasorelaxation and the expression of eNOS and the adrenoceptor activation at the doses below 10-6 mole/L in ZDF rats at 19 weeks of age. Rosi treatment for 3 weeks did not, however, improve the mechanical properties of blood vessel, the expressions of α-adrenoceptor, MMP9, and elastase in ZDF rats.ConclusionThe endothelial dysfunction and mechanical remodeling are observed as early as 19 weeks of age in ZDF rat. Rosi treatment for 3 weeks improves endothelial function but not mechanical properties.

【 授权许可】

Unknown   
© Lu et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.