title: Neurotransmission to parasympathetic cardiac vagal neurons in the brain stem is altered with left ventricular hypertrophy-induced heart failure.
abstract: Hypertension, cardiac hypertrophy, and heart failure (HF) are widespread and debilitating cardiovascular diseases that affect nearly 23 million people worldwide. A distinctive hallmark of these cardiovascular diseases is autonomic imbalance, with increased sympathetic activity and decreased parasympathetic vagal tone. Recent device-based approaches, such as implantable vagal stimulators that stimulate a multitude of visceral sensory and motor fibers in the vagus nerve, are being evaluated as new therapeutic approaches for these and other diseases. However, little is known about how parasympathetic activity to the heart is altered with these diseases, and this lack of knowledge is an obstacle in the goal of devising selective interventions that can target and selectively restore parasympathetic activity to the heart. To identify the changes that occur within the brain stem to diminish the parasympathetic cardiac activity, left ventricular hypertrophy was elicited in rats by aortic pressure overload using a transaortic constriction approach. Cardiac vagal neurons (CVNs) in the brain stem that generate parasympathetic activity to the heart were identified with a retrograde tracer and studied using patch-clamp electrophysiological recordings in vitro. Animals with left cardiac hypertrophy had diminished excitation of CVNs, which was mediated both by an augmented frequency of spontaneous inhibitory GABAergic neurotransmission (with no alteration of inhibitory glycinergic activity) as well as a diminished amplitude and frequency of excitatory neurotransmission to CVNs. Opportunities to alter these network pathways and neurotransmitter receptors provide future targets of intervention in the goal to restore parasympathetic activity and autonomic balance to the heart in cardiac hypertrophy and other cardiovascular diseases.
authors.affiliation: Department of Pharmacology and Physiology, The George Washington University, Washington, District of Columbia; and.
authors.forename: Edmund
authors.initials: E
authors.lastname: Cauley
authors.affiliation: Department of Pharmacology and Physiology, The George Washington University, Washington, District of Columbia; and.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pharmacology and Physiology, The George Washington University, Washington, District of Columbia; and.
authors.forename: Jhansi
authors.initials: J
authors.lastname: Dyavanapalli
authors.affiliation: Department of Pharmacology and Physiology, The George Washington University, Washington, District of Columbia; and.
authors.forename: Ke
authors.initials: K
authors.lastname: Sun
authors.affiliation: Department of Biomedical Engineering, The George Washington University, Washington, District of Columbia.
authors.forename: Kara
authors.initials: K
authors.lastname: Garrott
authors.affiliation: Department of Biomedical Engineering, The George Washington University, Washington, District of Columbia.
authors.forename: Sarah
authors.initials: S
authors.lastname: Kuzmiak-Glancy
authors.affiliation: Department of Biomedical Engineering, The George Washington University, Washington, District of Columbia.
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Kay
authors.affiliation: Department of Pharmacology and Physiology, The George Washington University, Washington, District of Columbia; and dmendel@gwu.edu.
authors.forename: David
authors.initials: D
authors.lastname: Mendelowitz
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D019706:Excitatory Postsynaptic Potentials; D059330:GABAergic Neurons / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D005998:Glycine / Q000378:metabolism; D006321:Heart / Q000294:innervation*; D006333:Heart Failure / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000150:complications* / Q000175:diagnosis / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D009433:Neural Inhibition; D009434:Neural Pathways / Q000378:metabolism / Q000503:physiopathology; D056347:Neuroanatomical Tract-Tracing Techniques; D018408:Patch-Clamp Techniques; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission; D014630:Vagus Nerve / Q000378:metabolism / Q000503:physiopathology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D005998:Glycine
keywords: autonomic; cardiac hypertrophy; heart failure; parasympathetic; vagal