title: Cardiovascular protective effects of nebivolol in Zucker diabetic fatty rats.
abstract: BACKGROUND
  Although effective in reducing blood pressure, therapy with a first-generation [beta]-blocker is currently controversial in metabolic syndrome due to its negative impact on carbohydrate and lipid metabolism.
  
  
  OBJECTIVE
  We evaluated the effects of nebivolol, a third-generation highly selective [beta]-blocker with additional vasodilating activity, versus the traditional [beta]-blocker atenolol in controlling functional and morphological cardiovascular damage in a rat model of metabolic syndrome.
  
  
  METHODS
  During 6 months, Zucker diabetic fatty (ZDF) rats and control lean Zucker rats (LZR) were studied. The experimental groups were: untreated ZDF, ZDF along with nebivolol, ZDF along with atenolol and LZR. Blood pressure, plasma insulin, triglycerides, cholesterol, glucose and platelet aggregation were evaluated. Malondialdehyde, reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio, CuZn superoxide dismutase, catalase and glutathione peroxidase were determined in heart homogenates and transforming growth factor [beta]1 and plasminogen activator inhibitor-1 (PAI-1) expression, by immunohistochemistry (IHC). Vascular reactivity, vascular cell adhesion molecule-1, platelet endothelial cell adhesion molecule-1, PAI-1, enhanced nitric oxide synthase and collagen expression were evaluated in aorta.
  
  
  RESULTS
  Nebivolol and atenolol presented a similar reduction in blood pressure. However, nebivolol showed a better lipid profile, preserved left ventricular function, a significant control in left ventricular geometry and moderated left ventricular hypertrophy versus atenolol. Significant reduction in platelet aggregation and a substantial endothelium-dependent and endothelium-independent relaxation in vessels were also shown in the nebivolol group versus atenolol group. Antioxidant defenses were preserved by nebivolol with a reduction in oxidative stress parameters. Vascular cell adhesion molecule-1, platelet endothelial cell adhesion molecule-1, PAI-1 and eNOS were favorably modulated with nebivolol in vessel wall. TGF[beta]1, PAI-1 and accumulation of collagen-III and collagen-I were also diminished in heart with nebivolol.
  
  
  CONCLUSIONS
  The present study provides substantial information supporting an actual protective role of nebivolol in comparison with atenolol in experimental metabolic syndrome.
authors.affiliation: Laboratory of Experimental Medicine, Hospital Alemán, Argentina. jorgetoblli@fibertel.com.ar
authors.forename: Jorge
authors.initials: J
authors.lastname: Toblli
authors.forename: Gabriel
authors.initials: G
authors.lastname: Cao
authors.forename: Carlos
authors.initials: C
authors.lastname: Rivas
authors.forename: Marina
authors.initials: M
authors.lastname: Munoz
authors.forename: Jorge
authors.initials: J
authors.lastname: Giani
authors.forename: Fernando
authors.initials: F
authors.lastname: Dominici
authors.forename: Margarita
authors.initials: M
authors.lastname: Angerosa
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000503:physiopathology; D001262:Atenolol / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000097:blood / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D024061:Collagen Type III / Q000378:metabolism; D004195:Disease Models, Animal; D004983:Ethanolamines / Q000494:pharmacology*; D017379:Hypertrophy, Left Ventricular / Q000517:prevention & control; D066298:In Vitro Techniques; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D000068577:Nebivolol; D018384:Oxidative Stress / Q000187:drug effects; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology*; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D000319:Adrenergic beta-Antagonists; D001578:Benzopyrans; D024061:Collagen Type III; D004983:Ethanolamines; D017395:Plasminogen Activator Inhibitor 1; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019010:Vascular Cell Adhesion Molecule-1; D014665:Vasodilator Agents; D000068577:Nebivolol; D001262:Atenolol