title: Celiprolol, a selective beta1-blocker, reduces the infarct size through production of nitric oxide in a rabbit model of myocardial infarction.
abstract: BACKGROUND
  It is still unclear whether celiprolol, a beta(1)-selective blocker, reduces myocardial infarct size. This study will examine whether celiprolol reduces myocardial infarct size, as well as investigate the mechanisms for its infarct size-reducing effect in rabbits.
  
  
  RESULTS
  Japanese white rabbits underwent 30 min of ischemia and 48 h of reperfusion. Celiprolol (1 or 10 mg x kg (-1) x h(-1) for 60 min, iv) was administered 20 min before ischemia with or without pretreatment with N(omega)-nitro-L-arginine methylester (L-NAME, 10 mg/kg, iv, a nitric oxide synthase inhibitor) or 5-hydroxydecanoic acid sodium salt (5-HD, 5 mg/kg, iv, a mitochondrial K(ATP) channel blocker). The area at risk as a percentage of the left ventricle was determined by using Evans blue dye, and the infarct size was determined as a percentage of the area at risk by triphenyl tetrazolium chloride staining. Celiprolol 1 and 10 mg x kg(-1) x h(-1) significantly reduced the infarct size in a dose-dependent manner (36.4+/-1.7%, n=7 and 25.4+/-2.9%, n=7, respectively) compared with the control (46.2+/-3.1%, n=8). The infarct size-reducing effect of celiprolol was completely blocked by L-NAME (40.4 +/-2.8%, n=8) but not by 5-HD (27.3+/-1.0%, n=8). Celiprolol 1 mg x kg(-1) x h (-1) increased the myocardial interstitial levels of NOx, an indicator of nitric oxide, and reduced the intensity of dihydro-ethidium staining of myocardium, an indicator of superoxide, during reperfusion after 30 min of ischemia.
  
  
  CONCLUSIONS
  Celiprolol reduces myocardial infarct size and also increases nitric oxide production and reduces superoxide levels but not mitochondrial K(ATP) channels in rabbits.
authors: Second Department of Internal Medicine, Gifu University School of Medicine.
authors: Xuehai
authors: X
authors: Chen
authors: Shinya
authors: S
authors: Minatoguchi
authors: Masazumi
authors: M
authors: Arai
authors: Ningyuan
authors: N
authors: Wang
authors: Cuanjiang
authors: C
authors: Lu
authors: Bao
authors: B
authors: Narentuoya
authors: Yoshihiro
authors: Y
authors: Uno
authors: Yu
authors: Y
authors: Misao
authors: Genzou
authors: G
authors: Takemura
authors: Takako
authors: T
authors: Fujiwara
authors: Hisayoshi
authors: H
authors: Fujiwara
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D017272:Celiprolol / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000502:physiology; D008297:Male; D008929:Mitochondria, Heart / Q000502:physiology; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D009206:Myocardium / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D015221:Potassium Channels / Q000502:physiology; D011817:Rabbits; D013481:Superoxides / Q000378:metabolism
chemical_list: D000319:Adrenergic beta-Antagonists; D015221:Potassium Channels; D013481:Superoxides; D009569:Nitric Oxide; D017272:Celiprolol