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.


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.


CONCLUSIONS
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.
Mercanoglu
Guldem
G
Department of Pharmacology, Faculty of Pharmacy, Yeditepe University, Kayisdagi, Istanbul, Turkey. guldemiko@yahoo.com
Safran
Nurhas
N
Gungor
Mehmet
M
Pamukcu
Burak
B
Uzun
Hafize
H
Sezgin
Can
C
Mercanoglu
Fehmi
F
Fici
Francesco
F
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001578:Benzopyrans / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D006152:Cyclic GMP / Q000097:blood; D004195:Disease Models, Animal; D004983:Ethanolamines / Q000494:pharmacology*; D008297:Male; D046529:Microscopy, Electron, Transmission; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D000068577:Nebivolol; D051381:Rats; D017207:Rats, Sprague-Dawley; D026361:Reactive Nitrogen Species / Q000097:blood; D016277:Ventricular Function, Left / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D001578:Benzopyrans; D004983:Ethanolamines; D026361:Reactive Nitrogen Species; D000068577:Nebivolol; D006152:Cyclic GMP