title: Rosiglitazone reverses endothelial dysfunction but not remodeling of femoral artery in Zucker diabetic fatty rats.
abstract: OBJECTIVE
  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 alpha-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), alpha-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 alpha-adrenoceptor was activated and the mechanical elastic modulus was increased in ZDF rats at 19 weeks of age. The expressions of alpha-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 alpha-adrenoceptor, MMP9, and elastase in ZDF rats.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Biomedical Engineering, Indiana University Purdue University, Indianapolis, IN 46202, USA.
authors.forename: Xiao
authors.initials: X
authors.lastname: Lu
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Guo
authors.forename: Sotirios K
authors.initials: SK
authors.lastname: Karathanasis
authors.forename: Karen M
authors.initials: KM
authors.lastname: Zimmerman
authors.forename: Jude E
authors.initials: JE
authors.lastname: Onyia
authors.forename: Richard G
authors.initials: RG
authors.lastname: Peterson
authors.forename: Ghassan S
authors.initials: GS
authors.lastname: Kassab
mesh_terms: D050154:Adiposity; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D005263:Femoral Artery / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009213:Myography; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010196:Pancreatic Elastase / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D013997:Time Factors; D014280:Triglycerides / Q000097:blood; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D011942:Receptors, Adrenergic, alpha; D045162:Thiazolidinediones; D014280:Triglycerides; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000077154:Rosiglitazone; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D010196:Pancreatic Elastase; D020780:Matrix Metalloproteinase 9