title: Improvement of left ventricular diastolic function induced by β-blockade: a comparison between nebivolol and metoprolol.
abstract: OBJECTIVE
  Enhanced adrenergic drive is involved in the development of left ventricular (LV) diastolic dysfunction observed in metabolic syndrome (MS). Thus, β-blockers might improve LV dysfunction observed in MS, but whether this occurs is unknown.
  
  
  METHODS
  We assessed in Zucker fa/fa rats the effects of short- (5 days) and long-term (90 days) metoprolol ('pure' β-blockade; 80 mg/kg/day) or nebivolol (β-blocker with vasodilating properties; 5mg/kg/day) treatment on LV hemodynamics and remodeling, as well as the long-term effects on coronary and peripheral endothelial dysfunction.
  
  
  RESULTS
  At identical degree of β(1)-receptor blockade, metoprolol and nebivolol decreased heart rate to the same extent and preserved cardiac output via increased stroke volume. None of the β-blockers, either after long- or short-term administration, modified LV end-systolic pressure-volume relation. Both β-blockers reduced, after long-term administration, LV end-diastolic pressure, Tau and end-diastolic pressure-volume relation, and this was associated with reduced LV collagen density, but not heart weight. Similar hemodynamic effects were also observed after short-term nebivolol, but not short-term metoprolol. These short-term effects of nebivolol were abolished by NO synthase inhibition. At the vascular level, nebivolol, and to a lesser extend metoprolol, improved NO dependent coronary vasorelaxation, which was abolished by NO synthase inhibition.
  
  
  CONCLUSIONS
  In a model of MS, the β-blockers metoprolol and nebivolol improve to the same extent LV hemodynamics, remodeling and diastolic function, but nebivolol prevent more markedly endothelium dependent vasorelaxation involving a more marked enhancement of NO bio-availability.
authors.affiliation: INSERM U644, Institut Fédératif de Recherches Multidisciplinaires sur les Peptides n°23 Institut de Recherche et d'Innovation Biomédicale de Haute Normandie, UFR de Médecine et de Pharmacie, Rouen, France.
authors.forename: Yuehua
authors.initials: Y
authors.lastname: Fang
authors.forename: Lionel
authors.initials: L
authors.lastname: Nicol
authors.forename: Najah
authors.initials: N
authors.lastname: Harouki
authors.forename: Christelle
authors.initials: C
authors.lastname: Monteil
authors.forename: Didier
authors.initials: D
authors.lastname: Wecker
authors.forename: Manuelle
authors.initials: M
authors.lastname: Debunne
authors.forename: Fabrice
authors.initials: F
authors.lastname: Bauer
authors.forename: Françoise
authors.initials: F
authors.lastname: Lallemand
authors.forename: Vincent
authors.initials: V
authors.lastname: Richard
authors.forename: Christian
authors.initials: C
authors.lastname: Thuillez
authors.forename: Paul
authors.initials: P
authors.lastname: Mulder
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects; D004983:Ethanolamines / Q000494:pharmacology* / Q000627:therapeutic use; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy / Q000378:metabolism; D008790:Metoprolol / Q000494:pharmacology* / Q000627:therapeutic use; D000068577:Nebivolol; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D014664:Vasodilation / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects*; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D001578:Benzopyrans; D004983:Ethanolamines; D000068577:Nebivolol; D009569:Nitric Oxide; D008790:Metoprolol