Carvedilol ameliorates the decreases in connexin 43 and ventricular fibrillation threshold in rats with myocardial infarction.
Connexin 43 (Cx43) is the most prominent connexin in the mammalian ventricular myocardium and forms gap junctions that are essential for normal conduction of action potential. Carvedilol, a nonselective beta-blocker, is widely used to prevent ventricular arrhythmias after myocardial infarction (MI). Here, we examined the effect of carvedilol on the expression of Cx43 protein and ventricular fibrillation threshold (VFT) using a rat MI model. VFT is defined as the lowest voltage, at which ventricular fibrillation is induced by electrical stimulation. Adult male Wister rats were divided into sham-operated group (n = 20) and MI groups treated with intragastric administration of saline (control, n = 30) or carvedilol (2.5 mg/kg, n = 30) twice a day for 7 days immediately after ligation of the left coronary artery. Compared with sham group (100%), total Cx43 protein and phosphorylated Cx43 protein were decreased in the MI rats to 60 +/- 21% and 52 +/- 19% (both P < 0.05), respectively. Treatment with carvedilol prevented the MI-induced decrease in total and phosphorylated Cx43 levels (91 +/- 17% and 80 +/- 20%, both P < 0.05), respectively, which were similar to the levels of sham animals. Moreover, the MI rats exhibited a marked decrease in VFT compared with the sham group (7.2 +/- 1.30 vs. 13.0 +/- 2.12 V, P < 0.05), but the decrease was abolished by carvedilol (11.0 +/- 2.65 V). In conclusion, carvedilol might prevent the ischemia-induced ventricular arrhythmias by restoring Cx43 protein and VFT to the basal levels.
Wen
Huazhi
H
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
Jiang
Hong
H
Lu
Zhibing
Z
He
Bo
B
Hu
Xiaorong
X
Chen
Jing
J
Zhao
Dongdong
D
D000818:Animals; D015153:Blotting, Western; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009203:Myocardial Infarction / Q000150:complications* / Q000378:metabolism* / Q000473:pathology; D010539:Permeability / Q000187:drug effects; D011412:Propanolamines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D014693:Ventricular Fibrillation / Q000150:complications* / Q000378:metabolism*
D002227:Carbazoles; D018031:Connexin 43; D011412:Propanolamines; D012333:RNA, Messenger; D000077261:Carvedilol