Beneficial Effect of Metoprolol is Associated with Increase of SIRT1 Activity in the Heart of Post Myocardial Infarction Rats

Beta-1 adrenergic receptor antagonists improve cardiac function in both animal models and patients with Heart Failure (HF). Sirtuin 1 (SIRT1), a NAD⁺-dependent deacetylases recognized to contrast aged-associated diseases, including HF could be involved in such effect.

Aim of this study was to investigate the involvement of SIRT1 in mediating the cardio protective effects of metoprolol.

Myocardial infarction (MI) was induced by cryoinfarction in adult rats. Metoprolol treatment was initiated 12 weeks post-MI till 24 weeks. Echocardiography was performed 12 and 24 weeks post-MI and hemodynamic parameters were measured at baseline and after maximal challenge with isoproterenol. At 12 weeks after MI, 20 rats were randomized to receive either saline solution or metoprolol. Sham animals represented a further control group. All groups were analysed by echocardiography to confirm the presence of similar levels of LV dysfunction and HF among randomized groups. A specific fluorimetric assay was used to measure SIRT1 activity in the hearts of the rats.

At the end of the study period HF groups showed a reduced ejection fraction (EF) and fractional shortening (FS) compared to sham animals (p<0.0001). Twelve weeks of metoprolol treatment resulted in a improvement in both EF and FS compared to HF rats treated with saline (p<0.01). The hemodynamics confirmed a metoprolol-dependent amelioration of cardiac contractility and relaxation. Twelve weeks of metoprolol treatment increased SIRT1 activity compared to both MI-saline and sham rats (both p<0.0001).

Metoprolol improved cardiac function in HF rats and this effect was associated with increased levels of SIRT1 activity.