Glucagon-like peptide-1 receptor (GLP-1 receptor) agonists are considered to exert cardioprotective effects in models of acute and chronic
heart disease. The present study aimed to investigate the role of
exendin-4 (a
GLP-1 receptor agonist) in atrial arrhythmogenesis in a model of
myocardial infarction (MI)-induced
heart failure and to elucidate the mechanisms underlying its effects. For this purpose, male Sprague-Dawley rats underwent
sham surgery or left anterior descending artery
ligation prior to being treated with saline/
exendin-4/
exendin-4 plus exendin9-39 (an antagonist of
GLP-1 receptor) for 4 weeks. The effects of
exendin-4 on atrial electrophysiology, atrial
fibrosis and PI3K/AKT signaling were assessed. Rats with MI exhibited depressed left ventricular function, an enlarged left atrium volume, prolonged action potential duration, elevated atrial
tachyarrhythmia inducibility, decreased conduction velocity and an increased total activation time, as well as total activation time dispersion and atrial
fibrosis. However, these abnormalities were attenuated by treatment with the
GLP-1 receptor agonist,
exendin-4. Moreover, the expression levels of
collagen I,
collagen III, transforming growth factor-β1, phosphorylated PI3K and AKT levels in atrial tissues were upregulated in rats with MI. These changes were also attenuated by
exendin-4. It was also found that these exedin-4-mediated attenutations were mitigated by the co-administration of exendin9-39 with
exendin-4. Overall, the findings of the present study suggested that
exendin-4 decreases susceptibility to atrial arrhythmogenesis, improves conduction properties and exerts antifibrotic effects via the
GLP-1 receptor signaling pathway. These findings provide evidence for the potential use of GLP-1R in the treatment of
atrial fibrillation.