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.