Effects of ghrelin on Cx43 regulation and electrical remodeling after myocardial infarction in rats.
Ghrelin is a novel growth hormone-releasing peptide, which has been shown to exert beneficial effects on ventricular remodeling. In this study, we investigated whether ghrelin could decrease vulnerability to ventricular arrhythmias in rats with myocardial infarction and the possible mechanism. Twenty-four hours after ligation of the anterior descending artery, adult male Sprague-Dawley rats were randomized to ghrelin (100 μg/kg) and saline (control group) for 4 weeks. Sham animals underwent thoracotomy and pericardiotomy, but not LAD ligation. Myocardial endothelin-1 (ET-1) levels were significantly elevated in saline-treated rats at the border zone compared with sham-operated rats. Myocardial connexin43 (Cx43) expression at the border zone was significantly decreased in saline-treated infarcted rats compared with sham-operated rats. Ghrelin significantly decreased the inducibility of ventricular tachyarrhythmias compared with control group. Arrhythmias sores during programmed stimulation in saline-treated rats were significantly higher than scores in those treated with ghrelin. The electrophysiological improvement of fatal ventricular tachyarrhythmias was accompanied with increased immunofluorescence-stained Cx43, myocardial Cx43 protein and mRNA levels in ghrelin treated rats. We also shown that ghrelin significantly decreased tissue ET-1 levels at the infarcted border zone. Thus, ghrelin showed the protective effect on ventricular arrhythmias after myocardial infarction. Although the precise mechanism by which ghrelin modulates the dephosphorylation of Cx43 remains unknown, it is most likely that the ghrelin increased expression of Cx43 through the inhibition of ET-1.
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China.
Ming-Jie
MJ
Yuan
He
H
Huang
Yan-Hong
YH
Tang
Gang
G
Wu
Yong-Wei
YW
Gu
Yong-Jun
YJ
Chen
Cong-Xin
CX
Huang
D000200:Action Potentials; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000150:complications / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D003331:Coronary Vessels / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D004562:Electrocardiography; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D054439:Ghrelin / Q000008:administration & dosage* / Q000378:metabolism / Q000627:therapeutic use; D008026:Ligation; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020257:Ventricular Remodeling / Q000187:drug effects
D018031:Connexin 43; D019332:Endothelin-1; D054439:Ghrelin; D012333:RNA, Messenger