title: Carvedilol ameliorates the decreases in connexin 43 and ventricular fibrillation threshold in rats with myocardial infarction.
abstract: 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.
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
authors.forename: Huazhi
authors.initials: H
authors.lastname: Wen
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.forename: Zhibing
authors.initials: Z
authors.lastname: Lu
authors.forename: Bo
authors.initials: B
authors.lastname: He
authors.forename: Xiaorong
authors.initials: X
authors.lastname: Hu
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Dongdong
authors.initials: D
authors.lastname: Zhao
mesh_terms: 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*
chemical_list: D002227:Carbazoles; D018031:Connexin 43; D011412:Propanolamines; D012333:RNA, Messenger; D000077261:Carvedilol