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.

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.

• Authors: Xuehai Chen, Shinya Minatoguchi, Masazumi Arai, Ningyuan Wang, Cuanjiang Lu, Bao Narentuoya, Yoshihiro Uno, Yu Misao, Genzou Takemura, Takako Fujiwara, Hisayoshi Fujiwara
• Journal: Circulation journal : official journal of the Japanese Circulation Society (Circ J) Vol. 71 Issue 4 Pg. 574-9 (Apr 2007) ISSN: 1346-9843 [Print] Japan
• PMID: 17384462 (Publication Type: Journal Article)

Chemical References

• Adrenergic beta-Antagonists
• Potassium Channels
• Superoxides
• Nitric Oxide
• Celiprolol

Topics

• Adrenergic beta-Antagonists (therapeutic use)
• Animals
• Blood Pressure (physiology)
• Celiprolol (therapeutic use)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Heart Rate (physiology)
• Male
• Mitochondria, Heart (physiology)
• Myocardial Infarction (drug therapy, metabolism, pathology)
• Myocardium (metabolism)
• Nitric Oxide (metabolism)
• Potassium Channels (physiology)
• Rabbits
• Superoxides (metabolism)