title: Autonomic cardiocirculatory control in mice with reduced expression of the vesicular acetylcholine transporter.
abstract: In cardiovascular diseases, sympathetic tone has been comprehensively studied, whereas parasympathetic tone has received minor attention. The vesicular ACh transporter (VAChT) knockdown homozygous (VAChT KD(HOM)) mouse is a useful model for examining the cardiocirculatory sympathovagal balance. Therefore, we investigated whether cholinergic dysfunction caused by reduced VAChT expression could adversely impact hemodynamic parameter [arterial pressure (AP) and heart rate (HR)] daily oscillation, baroreflex sensitivity, hemodynamic variability, sympathovagal balance, and cardiovascular reactivity to restraint stress. Wild-type and VAChT KD(HOM) mice were anesthetized for telemetry transmitter implantation, and APs and HRs were recorded 10 days after surgical recovery. Changes in HR elicited by methylatropine and propranolol provided the indexes of sympathovagal tone. Cardiovascular reactivity in response to a restraint test was examined 24 h after continuous recordings of AP and HR. VAChT KD(HOM) mice exhibited reduced parasympathetic and elevated sympathetic tone. Daily oscillations of AP and HR as well as AP variability were similar between groups. Nevertheless, HR variability, patterns with two dissimilar variations from symbolic analysis, and baroreflex sensitivity were reduced in VAChT KD(HOM) mice. The change in mean AP due to restraint stress was greater in VAChT KD(HOM) mice, whereas the tachycardic response was not. These findings demonstrate that the cholinergic dysfunction present in the VAChT KD(HOM) mouse did not adversely impact basal hemodynamic parameters but promoted autonomic imbalance, an attenuation of baroreflex sensitivity, and a greater pressure response to restraint stress. These results provide a framework for understanding how autonomic imbalance impacts cardiovascular function.
authors.affiliation: Department of Physiology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil;
authors.forename: Marina T
authors.initials: MT
authors.lastname: Durand
authors.affiliation: Department of Physiology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil;
authors.forename: Christiane
authors.initials: C
authors.lastname: Becari
authors.affiliation: Department of Physiology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil;
authors.forename: Geisa C S V
authors.initials: GC
authors.lastname: Tezini
authors.affiliation: Department of Physiology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil;
authors.forename: Rubens
authors.initials: R
authors.lastname: Fazan
authors.affiliation: Department of Physiology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil;
authors.forename: Mauro
authors.initials: M
authors.lastname: Oliveira
authors.affiliation: Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; and.
authors.forename: Silvia
authors.initials: S
authors.lastname: Guatimosim
authors.affiliation: Robarts Research Institute, Department of Anatomy and Cell Biology and Department of Physiology and Pharmacology, The University of Western Ontario, London, Ontario, Canada.
authors.forename: Vania F
authors.initials: VF
authors.lastname: Prado
authors.affiliation: Robarts Research Institute, Department of Anatomy and Cell Biology and Department of Physiology and Pharmacology, The University of Western Ontario, London, Ontario, Canada.
authors.forename: Marco A M
authors.initials: MA
authors.lastname: Prado
authors.affiliation: Department of Physiology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil; hcsalgado@fmrp.usp.br.
authors.forename: Helio C
authors.initials: HC
authors.lastname: Salgado
mesh_terms: D000200:Action Potentials; D000818:Animals; D062186:Arterial Pressure; D001341:Autonomic Nervous System / Q000378:metabolism* / Q000502:physiology; D017704:Baroreflex; D006321:Heart / Q000294:innervation / Q000502:physiology*; D006339:Heart Rate; D008297:Male; D051379:Mice; D009206:Myocardium / Q000378:metabolism; D050494:Vesicular Acetylcholine Transport Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C493460:Slc18a3 protein, mouse; D050494:Vesicular Acetylcholine Transport Proteins
keywords: daily hemodynamic oscillations; heart rate variability; mice; parasympathetic nervous system; vesicular acetylcholine transporter