title: 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.
authors: Department of Cardiology, First Affiliated Hospital, Harbin Medical University, Harbin, P.R. China.
authors: Li
authors: L
authors: Sheng
authors: Qiuling
authors: Q
authors: Shen
authors: Kan
authors: K
authors: Huang
authors: Guangzhong
authors: G
authors: Liu
authors: Jing
authors: J
authors: Zhao
authors: Wei
authors: W
authors: Xu
authors: Yixi
authors: Y
authors: Liu
authors: Weimin
authors: W
authors: Li
authors: Yue
authors: Y
authors: Li
mesh_terms: D058667:Adrenergic beta-3 Receptor Agonists / Q000494:pharmacology; D058673:Adrenergic beta-3 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D001281:Atrial Fibrillation / Q000378:metabolism / Q000503:physiopathology*; D016275:Atrial Function / Q000502:physiology*; D004285:Dogs; D004562:Electrocardiography; D006325:Heart Atria / Q000187:drug effects / Q000648:ultrastructure; D007150:Immunohistochemistry; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D022702:Receptors, Adrenergic, beta-3 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D058667:Adrenergic beta-3 Receptor Agonists; D058673:Adrenergic beta-3 Receptor Antagonists; D022702:Receptors, Adrenergic, beta-3; D048051:p38 Mitogen-Activated Protein Kinases