title: Leptin decreases heart rate associated with increased ventricular repolarization via its receptor.
abstract: Leptin has been proposed to modulate cardiac electrical properties via β-adrenergic receptor activation. The presence of leptin receptors and adipocytes in myocardium raised a question as to whether leptin can directly modulate cardiac electrical properties such as heart rate and QT interval via its receptor. In this work, the role of local direct actions of leptin on heart rate and ventricular repolarization was investigated. We identified the protein expression of leptin receptors at cell surface of sinus node, atrial, and ventricular myocytes isolated from rat heart. Leptin at low doses (0.1-30 μg/kg) decreased resting heart rate; at high doses (150-300 μg/kg), leptin induced a biphasic effect (decrease and then increase) on heart rate. In the presence of high-dose propranolol (30 mg/kg), high-dose leptin only reduced heart rate and sometimes caused sinus pauses and ventricular tachycardia. The leptin-induced inhibition of resting heart rate was fully reversed by leptin antagonist. Leptin also increased heart rate-corrected QT interval (QTc), and leptin antagonist did not. In isolated ventricular myocytes, leptin (0.03-0.3 μg/ml) reversibly increased the action potential duration. These results supported our hypothesis that in addition to indirect pathway via sympathetic tone, leptin can directly decrease heart rate and increase QT interval via its receptor independent of β-adrenergic receptor stimulation. During inhibition of β-adrenergic receptor activity, high concentration of leptin in myocardium can cause deep bradycardia, prolonged QT interval, and ventricular arrhythmias.
authors.affiliation: Graduate Institute of Biotechnology, Chinese Culture University, Taipei, Taiwan;
authors.forename: Yen-Chang
authors.initials: YC
authors.lastname: Lin
authors.affiliation: Center for Cardiovascular and Respiratory Sciences, Department of Physiology and Pharmacology, and.
authors.forename: Jianying
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Physiology and Pharmacology, and.
authors.forename: Stan
authors.initials: S
authors.lastname: Hileman
authors.affiliation: Mary Babb Randolph Cancer Center and Department of Neurobiology and Anatomy, Department of Cardiology and Heart Institute of Health Sciences Center, and.
authors.forename: Karen H
authors.initials: KH
authors.lastname: Martin
authors.affiliation: Heart Institute, West Virginia University, Morgantown, West Virginia.
authors.forename: Robert
authors.initials: R
authors.lastname: Hull
authors.affiliation: Department of Physiology and Pharmacology, and.
authors.forename: Mary
authors.initials: M
authors.lastname: Davis
authors.affiliation: Center for Cardiovascular and Respiratory Sciences, Department of Physiology and Pharmacology, and hyu@hsc.wvu.edu.
authors.forename: Han-Gang
authors.initials: HG
authors.lastname: Yu
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D055724:Electrophysiological Phenomena / Q000187:drug effects; D006321:Heart / Q000187:drug effects; D006325:Heart Atria / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects*; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020738:Leptin / Q000378:metabolism / Q000494:pharmacology*; D008856:Microscopy, Fluorescence; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011924:Rats, Zucker; D054411:Receptors, Leptin / Q000378:metabolism*; D012849:Sinoatrial Node / Q000187:drug effects* / Q000378:metabolism; D017180:Tachycardia, Ventricular
chemical_list: D000319:Adrenergic beta-Antagonists; D020738:Leptin; D054411:Receptors, Leptin; D011433:Propranolol
keywords: QT interval; leptin; leptin receptor; resting heart rate