Norepinephrine-Induced Adrenergic Activation Strikingly Increased the Atrial Fibrillation Duration through β1- and α1-Adrenergic Receptor-Mediated Signaling in Mice

• Published in: PloS one 2015-07, Vol.10 (7), p.e0133664-e0133664
• Main Authors: Suita, Kenji, Fujita, Takayuki, Hasegawa, Nozomi, Cai, Wenqian, Jin, Huiling, Hidaka, Yuko, Prajapati, Rajesh, Umemura, Masanari, Yokoyama, Utako, Sato, Motohiko, Okumura, Satoshi, Ishikawa, Yoshihiro
• Format: Article
• Language: English
• Subjects: Adrenergic alpha-Antagonists - pharmacology; Adrenergic beta-Antagonists - pharmacology; Adrenergic receptors; Animals; Atrial Fibrillation - chemically induced; Atrial Fibrillation - physiopathology; Calcium Signaling - drug effects; Cardiac arrhythmia; Cardiomyocytes; Catecholamines; Cells, Cultured; Disease Models, Animal; Health problems; Heart Conduction System - drug effects; Heart Conduction System - physiopathology; Injection; Injections, Intraperitoneal; Kinases; Male; Medicine; Metoprolol - pharmacology; Mice; Mice, Inbred C57BL; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - physiology; Nervous system; Norepinephrine; Norepinephrine - administration & dosage; Norepinephrine - toxicity; Older people; Physiology; Prazosin - pharmacology; Quality of life; Receptors, Adrenergic, alpha-1 - drug effects; Receptors, Adrenergic, alpha-1 - physiology; Receptors, Adrenergic, beta-1 - drug effects; Receptors, Adrenergic, beta-1 - physiology; Rodents; Sarcoplasmic Reticulum - drug effects; Studies; Sympathetic Nervous System - drug effects; Sympathetic Nervous System - physiopathology; Therapeutic applications; University graduates
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0133664

Atrial fibrillation (AF) is the most common arrhythmias among old people. It causes serious long-term health problems affecting the quality of life. It has been suggested that the autonomic nervous system is involved in the onset and maintenance of AF in human. However, investigation of its pathogenesis and potential treatment has been hampered by the lack of suitable AF models in experimental animals. Our aim was to establish a long-lasting AF model in mice. We also investigated the role of adrenergic receptor (AR) subtypes, which may be involved in the onset and duration of AF. Trans-esophageal atrial burst pacing in mice could induce AF, as previously shown, but with only a short duration (29.0 ± 8.1 sec). We found that adrenergic activation by intraperitoneal norepinephrine (NE) injection strikingly increased the AF duration. It increased the duration to more than 10 minutes, i.e., by more than 20-fold (656.2 ± 104.8 sec; P