The effects of nebivolol on apoptosis in a rat infarct model

Background: In the present study, nitric oxide (NO) was investigated to see if it mediated effects of nebivolol on apoptosis in the rat myocardial infarction (MI) model. Methods and Results: Rats were divided into 3 groups: sham operated (sham-control), MI-induced (MI-control) and nebivolol treated (MI-nebivolol). The initial dose of nebivolol was administrated intravenously (iv) within 10min of post-MI reperfusion and continued orally for 28 days. NO mediated effects of nebivolol were assessed either in the early (2nd day) or sub-acute (28th day) period of MI by histologic, hemodynamic and biologic studies. Left ventricular (LV) pressure changes were prevented with nebivolol (the increase in LV end-diastolic pressure and the decrease in maximum rise and fall rate of LV pressure (+dp/dt and -dp/dt) was significantly less in MI-nebivolol). Total and regional apoptotic indexes were significantly lower in the MI-nebivolol group (10.2 vs 7.1%, respectively on the 2 nd day; p=0.004). Although plasma nitrite/nitrate, cyclic guanylate cyclase and peroxynitrite concentrations were high both in Mi-control and MI-nebivolol groups on the 2nd day, these concentrations were decreased to the basal value on the 28th day in the MI-nebivolol group. Conclusion: As a result, nebivolol treatment (initially by iv within 10min of reperfusion and continued orally) reduced the myocardial apoptosis after MI. This beneficial effect of nebivolol is mediated by NO regulation.