title: Nitric oxide mediated effects of nebivolol in myocardial infarction: the source of nitric oxide.
abstract: OBJECTIVE
  After MI pathological LV remodeling is one of the major causes of death. We previously showed the NO mediated beneficial effects of nebivolol in rat MI model, in this study we aimed to evaluate the NOS related mechanisms in this phenomenon.
  
  
  METHODS
  Rats were divided into four groups: sham operated (sham-control), MI-induced (MI-control), immediate nebivolol loaded (MI-neb1), orally nebivolol treated (MI-neb2). MI was induced by the ligation of the LAD. Loading dose of nebivolol (0.1 mg/kg) was administrated i.v. during reperfusion and continuation dose was administrated orally (2 mg/kg) by gastric gavages once daily. NOS related mechanisms were assessed either in acute (2nd day) and sub-acute (28th day) period of MI by histologic, hemodynamic and biologic studies.
  
  
  RESULTS
  Compared to MI-control rats, physiological functions of LV (LVEDP, Δ±dp/dt) were prevented in both nebivolol treated groups. Improvements in anatomical parameters (LEV, HW, LVW/HW) were consistent with functional improvement too. Moreover, oxidative (characterized by decreased MDA and increased SOD levels) and nitrosative (characterized by decreased ONOO- levels) damage were limited in these groups. Compared to MI-control rats, most marked change was seen in the nNOS labelling in the nebivolol treated groups. The decrease in iNOS labelling was also prominent in these groups too.
  
  
  CONCLUSIONS
  NOS mediated mechanisms of nebivolol can be summarized as: 1) diminishing iNOS expression together with restoration of MI induced eNOS activation both in vascular bed and myocytes at the acute period of MI, and 2) prevention of deterioration in nNOS expression in myocardial cells at the sub-acute period of MI.
authors.affiliation: Department of Pharmacology, Biruni University, Faculty of Pharmacy, Istanbul, Turkey. guldemiko@gmail.com.
authors.forename: G
authors.initials: G
authors.lastname: Mercanoglu
authors.forename: N
authors.initials: N
authors.lastname: Safran
authors.forename: B
authors.initials: B
authors.lastname: Ahishali B
authors.forename: H
authors.initials: H
authors.lastname: Uzun
authors.forename: A
authors.initials: A
authors.lastname: Yalcin
authors.forename: F
authors.initials: F
authors.lastname: Mercanoglu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004195:Disease Models, Animal; D006439:Hemodynamics / Q000187:drug effects; D007262:Infusions, Intravenous; D008297:Male; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D000068577:Nebivolol / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000097:blood; D052247:Nitric Oxide Synthase Type II / Q000097:blood; D052250:Nitric Oxide Synthase Type III / Q000097:blood; D051381:Rats; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D014665:Vasodilator Agents; D000068577:Nebivolol; D009569:Nitric Oxide; C496320:NOS1 protein, human; C496319:NOS2 protein, human; C496314:NOS3 protein, human; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III