Celiprolol, a Selective .BETA.1-Blocker, Reduces the Infarct Size Through Production of Nitric Oxide in a Rabbit Model of Myocardial Infarction

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. METHODS AND 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. CONCLUSION: Celiprolol reduces myocardial infarct size and also increases nitric oxide production and reduces superoxide levels but not mitochondrial K(ATP) channels in rabbits.