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Nebivolol Exerts Beneficial Effects on Endothelial Function, Early Endothelial Progenitor Cells, Myocardial Neovascularization, and Left Ventricular Dysfunction Early After Myocardial Infarction Beyond Conventional β(1)-Blockade.
MedLine Citation:
PMID:  21272752     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
OBJECTIVES: The aim of this study was to investigate whether nebivolol has added effects on left ventricular (LV) dysfunction and remodeling early after myocardial infarction (MI) beyond its β(1)-receptor-blocking properties.
BACKGROUND: Nebivolol is a third-generation selective β(1)-adrenoreceptor antagonist that stimulates endothelial cell nitric oxide (NO) production and prevents vascular reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation. Both endothelial NO synthase-derived NO production and NADPH oxidase activation are critical modulators of LV dysfunction early after MI.
METHODS: Mice with extensive anterior MI (n = 90) were randomized to treatment with nebivolol (10 mg/kg/day), metoprolol-succinate (20 mg/kg/day), or placebo for 30 days starting on day 1 after surgery.
RESULTS: Infarct size was similar among the groups. Both β(1)-adrenergic receptor antagonists caused a similar decrease in heart rate. Nebivolol therapy improved endothelium-dependent vasorelaxation and increased early endothelial progenitor cells 4 weeks after MI compared with metoprolol and placebo. Nebivolol, but not metoprolol, inhibited cardiac NADPH oxidase activation after MI, as detected by electron spin resonance spectroscopy analysis. Importantly, nebivolol, but not metoprolol, improved LV dysfunction 4 weeks after MI (LV ejection fraction: nebivolol vs. metoprolol vs. placebo: 32 ± 4% vs. 17 ± 6% vs. 19 ± 4%; nebivolol vs. metoprolol: p < 0.05) and was associated with improved survival 4 weeks post-MI compared with placebo. Nebivolol had a significantly more pronounced inhibitory effect on cardiomyocyte hypertrophy after MI compared with metoprolol.
CONCLUSIONS: Nebivolol improves LV dysfunction and survival early after MI likely beyond the effects provided by conventional β(1)-receptor blockade. Nebivolol induced effects on NO-mediated endothelial function, early endothelial progenitor cells and inhibition of myocardial NADPH oxidase likely contribute to these beneficial effects of nebivolol early after MI.
Authors:
Sajoscha A Sorrentino; Carola Doerries; Costantina Manes; Thimoteus Speer; Chantal Dessy; Irina Lobysheva; Wazma Mohmand; Razma Akbar; Ferdinand Bahlmann; Christian Besler; Arnd Schaefer; Denise Hilfiker-Kleiner; Thomas F Lüscher; Jean-Luc Balligand; Helmut Drexler; Ulf Landmesser
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of the American College of Cardiology     Volume:  57     ISSN:  1558-3597     ISO Abbreviation:  J. Am. Coll. Cardiol.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8301365     Medline TA:  J Am Coll Cardiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  601-11     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Affiliation:
Division of Cardiology and Angiology, Medical School of Hannover, Hannover, Germany; Division of Nephrology, Medical School of Hannover, Hannover, Germany.
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