title: Cholinergic activity as a new target in diseases of the heart.
abstract: The autonomic nervous system is an important modulator of cardiac signaling in both health and disease. In fact, the significance of altered parasympathetic tone in cardiac disease has recently come to the forefront. Both neuronal and nonneuronal cholinergic signaling likely play a physiological role, since modulating acetylcholine (ACh) signaling from neurons or cardiomyocytes appears to have significant consequences in both health and disease. Notably, many of these effects are solely due to changes in cholinergic signaling, without altered sympathetic drive, which is known to have significant adverse effects in disease states. As such, it is likely that enhanced ACh-mediated signaling not only has direct positive effects on cardiomyocytes, but it also offsets the negative effects of hyperadrenergic tone. In this review, we discuss recent studies that implicate ACh as a major regulator of cardiac remodeling and provide support for the notion that enhancing cholinergic signaling in human patients with cardiac disease can reduce morbidity and mortality. These recent results support the idea of developing large clinical trials of strategies to increase cholinergic tone, either by stimulating the vagus or by increased availability of Ach, in heart failure.
authors.affiliation: Robarts Research Institute, The University of Western Ontario, London, Ontario, Canada.|Department of Physiology and Pharmacology, The University of Western Ontario, London, Ontario, Canada.
authors.forename: Ashbeel
authors.initials: A
authors.lastname: Roy
authors.affiliation: Department of Physiology and Biophysics, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Silvia
authors.initials: S
authors.lastname: Guatimosim
authors.affiliation: Robarts Research Institute, The University of Western Ontario, London, Ontario, Canada.|Department of Physiology and Pharmacology, The University of Western Ontario, London, Ontario, Canada.|Department of Anatomy and Cell Biology, The University of Western Ontario, London, Ontario, Canada.
authors.forename: Vania F
authors.initials: VF
authors.lastname: Prado
authors.affiliation: Robarts Research Institute, The University of Western Ontario, London, Ontario, Canada.|Department of Physiology and Pharmacology, The University of Western Ontario, London, Ontario, Canada.|Department of Medicine, University of Western Ontario, London, Ontario, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Gros
authors.affiliation: Robarts Research Institute, The University of Western Ontario, London, Ontario, Canada.|Department of Physiology and Pharmacology, The University of Western Ontario, London, Ontario, Canada.|Department of Anatomy and Cell Biology, The University of Western Ontario, London, Ontario, Canada.
authors.forename: Marco A M
authors.initials: MA
authors.lastname: Prado
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001341:Autonomic Nervous System; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use; D006331:Heart Diseases / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans
chemical_list: D002800:Cholinesterase Inhibitors; D000109:Acetylcholine