Document Detail


Cardiovascular protective effects of nebivolol in Zucker diabetic fatty rats.
MedLine Citation:
PMID:  20411618     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 AND DESIGN: 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. CONCLUSION: The present study provides substantial information supporting an actual protective role of nebivolol in comparison with atenolol in experimental metabolic syndrome.
Authors:
Jorge Toblli; Gabriel Cao; Carlos Rivas; Marina Munoz; Jorge Giani; Fernando Dominici; Margarita Angerosa
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Publication Detail:
Type:  Comparative Study; In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of hypertension     Volume:  28     ISSN:  1473-5598     ISO Abbreviation:  J. Hypertens.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-04-21     Completed Date:  2010-07-29     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8306882     Medline TA:  J Hypertens     Country:  England    
Other Details:
Languages:  eng     Pagination:  1007-19     Citation Subset:  IM    
Affiliation:
Laboratory of Experimental Medicine, Hospital Alemán, Argentina. jorgetoblli@fibertel.com.ar
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MeSH Terms
Descriptor/Qualifier:
Adrenergic beta-Antagonists / pharmacology*
Animals
Antigens, CD31 / metabolism
Aorta / drug effects,  physiopathology
Atenolol / pharmacology
Benzopyrans / pharmacology*
Blood Pressure / drug effects
Cardiovascular Diseases / blood,  pathology,  physiopathology,  prevention & control*
Collagen Type III / metabolism
Disease Models, Animal
Ethanolamines / pharmacology*
Hypertrophy, Left Ventricular / prevention & control
Male
Metabolic Syndrome X / blood,  drug therapy*,  pathology,  physiopathology
Oxidative Stress / drug effects
Plasminogen Activator Inhibitor 1 / metabolism
Platelet Aggregation / drug effects
Rats
Rats, Zucker
Vascular Cell Adhesion Molecule-1 / metabolism
Vasodilator Agents / pharmacology*
Ventricular Function, Left / drug effects
Chemical
Reg. No./Substance:
0/Adrenergic beta-Antagonists; 0/Antigens, CD31; 0/Benzopyrans; 0/Collagen Type III; 0/Ethanolamines; 0/Plasminogen Activator Inhibitor 1; 0/Vascular Cell Adhesion Molecule-1; 0/Vasodilator Agents; 29122-68-7/Atenolol; 99200-09-6/nebivolol

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