The effects of nebivolol on apoptosis in a rat infarct model

  • Circ J. 2008 Apr;72(4):660-70. doi: 10.1253/circj.72.660.
Guldem Mercanoglu  1 ,  Nurhas Safran ,  Mehmet Gungor ,  Burak Pamukcu ,  Hafize Uzun ,  Can Sezgin ,  Fehmi Mercanoglu ,  Francesco Fici
Affiliations
  • 1. Department of Pharmacology, Faculty of Pharmacy, Yeditepe University, Kayisdagi, Istanbul, Turkey. [email protected]
PMID: 18362441 DOI: 10.1253/circj.72.660
Abstract

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 10 min of post-MI reperfusion and continued orally for 28 days. NO mediated effects of nebivolol were assessed either in the early (2(nd) day) or sub-acute (28(th) 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 2(nd) day, these concentrations were decreased to the basal value on the 28(th) day in the MI-nebivolol group.

Conclusion: As a result, nebivolol treatment (initially by iv within 10 min of reperfusion and continued orally) reduced the myocardial Apoptosis after MI. This beneficial effect of nebivolol is mediated by NO regulation.

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