Rosiglitazone reverses endothelial dysfunction but not remodeling of femoral artery in Zucker diabetic fatty rats
Autor: | Sotirios K. Karathanasis, Richard G. Peterson, Xiao Lu, Karen M. Zimmerman, Jude E Onyia, Xiaomei Guo, Ghassan S. Kassab |
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Jazyk: | angličtina |
Rok vydání: | 2010 |
Předmět: |
Blood Glucose
lcsh:Diseases of the circulatory (Cardiovascular) system Time Factors endocrine system diseases Endocrinology Diabetes and Metabolism Vasodilator Agents Vasodilation Blood Pressure Femoral artery Enos Vasoconstrictor Agents Endothelial dysfunction Adiposity biology Pancreatic Elastase Femoral Artery medicine.anatomical_structure Matrix Metalloproteinase 9 medicine.symptom Rosiglitazone Cardiology and Cardiovascular Medicine Blood vessel medicine.drug medicine.medical_specialty Nitric Oxide Synthase Type III medicine.artery Internal medicine medicine Animals Hypoglycemic Agents Triglycerides Original investigation Dose-Response Relationship Drug business.industry Body Weight Myography nutritional and metabolic diseases Receptors Adrenergic alpha medicine.disease biology.organism_classification Rats Rats Zucker Disease Models Animal Endocrinology Diabetes Mellitus Type 2 lcsh:RC666-701 Vasoconstriction Thiazolidinediones Endothelium Vascular business Diabetic Angiopathies Myograph |
Zdroj: | Cardiovascular Diabetology Cardiovascular Diabetology, Vol 9, Iss 1, p 19 (2010) |
ISSN: | 1475-2840 |
Popis: | Objectives Endothelial 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. Methods The 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. Results Endothelium-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. Conclusion The 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. |
Databáze: | OpenAIRE |
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