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

被引：132

作者：

Sorrentino, Sajoscha A. ^{[2
,3
]}

Doerries, Carola ^{[1
,2
]}

Manes, Costantina ^{[1
,2
]}

Speer, Thimoteus ^{[1
]}

Dessy, Chantal ^{[4
]}

Lobysheva, Irina ^{[4
]}

Mohmand, Wazma ^{[2
]}

Akbar, Razma ^{[2
]}

Bahlmann, Ferdinand ^{[3
]}

Besler, Christian ^{[1
,2
]}

Schaefer, Arnd ^{[2
]}

Hilfiker-Kleiner, Denise ^{[2
]}

Luescher, Thomas F. ^{[1
]}

Balligand, Jean-Luc ^{[4
]}

Drexler, Helmut ^{[2
]}

Landmesser, Ulf ^{[1
,2
]}

机构：

[1] Univ Zurich, Univ Zurich Hosp, Ctr Cardiovasc, Inst Physiol, CH-8091 Zurich, Switzerland

[2] Hannover Med Sch, Div Cardiol & Angiol, D-3000 Hannover, Germany

[3] Hannover Med Sch, Div Nephrol, D-3000 Hannover, Germany

[4] Univ Louvain, Sch Med, Unit Pharmacol & Therapeut, Brussels, Belgium

来源：

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY | 2011年 / 57卷 / 05期

基金：

瑞士国家科学基金会;

关键词：

beta-adrenoreceptor blocker; early endothelial progenitor cells; endothelial function; left ventricular remodeling; myocardial infarction; NITRIC-OXIDE SYNTHASE; 3RD-GENERATION BETA-BLOCKER; TYPE-2; DIABETES-MELLITUS; OXIDATIVE STRESS; NADPH OXIDASE; BONE-MARROW; CARDIAC-HYPERTROPHY; ANGIOTENSIN-II; MICE LACKING; EX-VIVO;

D O I：

10.1016/j.jacc.2010.09.037

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

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 beta(1)-receptor-blocking properties. Background Nebivolol is a third-generation selective beta(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 beta(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 beta(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. (J Am Coll Cardiol 2011;57:601-11) (C) 2011 by the American College of Cardiology Foundation

引用

页码：601 / 611

页数：11

共 48 条

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