Abstract 1869: Effect of Nebivolol vs. Metoprolol on Endothelial Function, Endothelial Progenitor Cell Mobilization and Left Ventricular Remodeling and Dysfunction Early After Myocardial Infarction
Introduction: Recent studies have suggested a protective role of endothelial nitric oxide synthase (eNOS)-dependent nitric oxide (NO) production on left ventricular (LV) remodeling and dysfunction after myocardial infarction (MI).
Hypothesis: We therefore compared the effect of Nebivolol, an eNOS-stimulating beta-blocker, and Metoprolol succinate on endothelium-dependent, NO-mediated vasodilatation, endothelial progenitor cell (EPC) mobilization, cardiomyocyte hypertrophy, interstitial fibrosis and LV-dysfunction post-MI as compared to Metoprolol succinate.
Methods and Results: Mice with extensive anterior MI were randomized to treatment with Nebivolol (10 mgxkg−1xd−1), Metoprolol succinate (20mgxkg−1xd−1), or Placebo via gavage for 30 days starting on day 1 after surgery. Infarct size was similar among the groups and both beta-blockers caused similar decrease in heart rate. Nebivolol improved endothelial function of aortic ring segments 4 weeks post-MI (vasorelaxation Nebi vs. Placebo 55±7 vs. 21±4%; P<0.05), whereas Metoprolol had no effect (Meto 21±1%; P=n.s. vs. Placebo). Nebivolol treatment, but not Metoprolol, caused an increased EPC mobilization (Nebivolol vs. Metoprolol vs. Placebo: 238±29 vs. 110±36 vs. 120±24 cells per hpf; P<0.05 Nebi vs. Meto & Placebo). After 4 week treatment, Nebivolol improved LV-dysfunction as assessed by echocardiography, while Metoprolol had no significant effect (LV-ejection fraction: Nebi vs. Meto vs. placebo 26±3 vs. 18±3 vs. 15±2; Nebi vs. placebo: P<0.05). Nebivolol had a more pronounced effect on cardiomyocyte hypertrophy and interstitial fibrosis as assessed by histomorphometric analysis. Moreover, Nebivolol, but not Metoprolol, improved post-MI survival as compared to Placebo.
Conclusions: In conclusion, the present findings suggest that Nebivolol, but not Metoprolol, improves endothelium-dependent vasodilatation, EPC mobilization and survival in mice post-MI. At equivalent myocardial beta-blocking doses, Nebivolol had a more pronounced effect on cardiomyocyte hypertrophy, interstitial fibrosis and LV-dysfunction post-MI, compatible with notion that Nebivolol may exert beneficial effects on LV-function early post-MI independent of its beta1-receptor blockade.