title: β2 adrenergic receptor activation governs cardiac repolarization and arrhythmogenesis in a guinea pig model of heart failure.
abstract: β2-AR activation increases the risk of sudden cardiac death (SCD) in heart failure (HF) patients. Non-selective β-AR blockers have greater benefits on survival than selective β1-AR blockers in chronic HF patients, indicating that β2-AR activation contributes to SCD in HF. This study investigated the role of β2-AR activation on repolarization and ventricular arrhythmia (VA) in the experimental HF model. The guinea pig HF was induced by descending aortic banding. The effective refractoriness period (ERP), corrected QT (QTc) and the incidence of VA were examined using Langendorff and programmed electrical stimulation. Ikr and APD were recorded by the whole cell patch clamp. Selective β2-AR agonist salbutamol significantly increased the incidence of VA, prolonged QTc and shortened ERP. These effects could be prevented by the selective β2-AR antagonist, ICI118551. Salbutamol prolonged APD90 and reduced Ikr in guinea pig HF myocytes. The antagonists of cAMP (Rp-cAMP) and PKA (KT5720) attenuated Ikr inhibition and APD prolongation induced by salbutamol. However, the antagonists of Gi protein (PTX) and PDE III (amrinone) showed opposite effects. This study indicates that β2-AR activation increases the incidence of VA in the experimental HF model via activation of Gs/cAMP/PKA and/or inhibition of Gi/PDE pathways.
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Jiamin
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Qian
authors.affiliation: Department of Cardiology, Huai'an First People's Hospital Affiliated to Nanjing Medical University, Huai'an, Jiangsu, China.
authors.forename: Xiwen
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Hou
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Jiangang
authors.initials: J
authors.lastname: Zou
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000420:Albuterol / Q000494:pharmacology; D000676:Amrinone / Q000494:pharmacology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000453:epidemiology / Q000209:etiology; D002227:Carbazoles / Q000494:pharmacology; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004562:Electrocardiography; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000037:antagonists & inhibitors / Q000378:metabolism; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000037:antagonists & inhibitors / Q000378:metabolism; D006168:Guinea Pigs; D006333:Heart Failure / Q000378:metabolism / Q000473:pathology*; D066298:In Vitro Techniques; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011758:Pyrroles / Q000494:pharmacology; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D013873:Thionucleotides / Q000494:pharmacology; D016276:Ventricular Function / Q000187:drug effects / Q000502:physiology
chemical_list: D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011758:Pyrroles; D018343:Receptors, Adrenergic, beta-2; D013873:Thionucleotides; C016957:adenosine-3',5'-cyclic phosphorothioate; C057416:KT 5720; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D019205:GTP-Binding Protein alpha Subunits, Gs; D000676:Amrinone; D000420:Albuterol