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J Mol Cell Cardiol. 2011 Aug;51(2):168-76. doi: 10.1016/j.yjmcc.2011.05.012. Epub 2011 May 24.

Improvement of left ventricular diastolic function induced by β-blockade: a comparison between nebivolol and metoprolol.

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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.



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.


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.


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.


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.

[Indexed for MEDLINE]

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