Upregulation of β3-Adrenergic Receptors Contributes to Atrial Structural Remodeling in Rapid Pacing Induced Atrial Fibrillation Canines

Abstract

Accumulating evidence suggests that the adrenergic receptors (ARs) play an important role in cardiac diseases. The expression of β3-AR has been recently demonstrated in atria, however, its role in atrial structural remodeling of atrial fibrillation (AF) is unclear. Therefore, the present study was designed to investigate the role of β3-AR in atrial structural remodeling in AF and to clarify its possible mechanisms. Twenty-eight dogs were randomly divided into sham, pacing, β3-AR agonist (BRL37344) and β3-AR antagonist (L748337) groups. AF was induced by rapid atrial pacing at 600 beats per minute for 3 weeks and evaluated by determining the ultrastructure and function of atria. The expression of β3-AR and p38 mitogen-activated protein kinase (MAPK) was examined by western blot, immunohistochemistry and real-time RT-PCR. Additionally, the extent of oxidative stress was tested. We found the atrial enlargement and dysfunction in pacing group. Moreover, atrial interstitial fibrosis, apoptosis and oxidative stress were increased and the levels of β3-AR and phosphorylated p38 MAPK were increased after pacing. Activation of β3-AR exacerbated the pathologic changes and oxidative stress, which were effectively inhibited by L748337. We concluded that β3-AR was upregulated in paced atria, which contributed to oxidative stress and exacerbated atrial structural remodeling by regulating p38 MAPK. Our study provides novel insights into the pharmacological role of β3-AR in AF.