title: Nebivolol exerts beneficial effects on endothelial function, early endothelial progenitor cells, myocardial neovascularization, and left ventricular dysfunction early after myocardial infarction beyond conventional β1-blockade.
abstract: OBJECTIVE
  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 β₁-receptor-blocking properties.
  
  
  BACKGROUND
  Nebivolol is a third-generation selective β₁-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 β₁-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 β₁-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.affiliation: Medical School of Hannover, Germany.
authors.forename: Sajoscha A
authors.initials: SA
authors.lastname: Sorrentino
authors.forename: Carola
authors.initials: C
authors.lastname: Doerries
authors.forename: Costantina
authors.initials: C
authors.lastname: Manes
authors.forename: Thimoteus
authors.initials: T
authors.lastname: Speer
authors.forename: Chantal
authors.initials: C
authors.lastname: Dessy
authors.forename: Irina
authors.initials: I
authors.lastname: Lobysheva
authors.forename: Wazma
authors.initials: W
authors.lastname: Mohmand
authors.forename: Razma
authors.initials: R
authors.lastname: Akbar
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Bahlmann
authors.forename: Christian
authors.initials: C
authors.lastname: Besler
authors.forename: Arnd
authors.initials: A
authors.lastname: Schaefer
authors.forename: Denise
authors.initials: D
authors.lastname: Hilfiker-Kleiner
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Lüscher
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Balligand
authors.forename: Helmut
authors.initials: H
authors.lastname: Drexler
authors.forename: Ulf
authors.initials: U
authors.lastname: Landmesser
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000627:therapeutic use*; D000818:Animals; D001578:Benzopyrans / Q000627:therapeutic use*; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D004983:Ethanolamines / Q000627:therapeutic use*; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D000068577:Nebivolol; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D011897:Random Allocation; D051381:Rats; D013997:Time Factors; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D001578:Benzopyrans; D004983:Ethanolamines; D000068577:Nebivolol