title: Origins of the vagal drive controlling left ventricular contractility.
abstract: The strength, functional significance and origins of parasympathetic innervation of the left ventricle remain controversial. This study tested the hypothesis that parasympathetic control of left ventricular contractility is provided by vagal preganglionic neurones of the dorsal motor nucleus (DVMN). Under β-adrenoceptor blockade combined with spinal cord (C1) transection (to remove sympathetic influences), systemic administration of atropine increased left ventricular contractility in rats anaesthetized with urethane, confirming the existence of a tonic inhibitory muscarinic influence on cardiac inotropy. Increased left ventricular contractility in anaesthetized rats was observed when DVMN neurones were silenced. Functional neuroanatomical mapping revealed that vagal preganglionic neurones that have an impact on left ventricular contractility are located in the caudal region of the left DVMN. These neurones provide functionally significant parasympathetic control of left ventricular inotropy.
  
  
  
  The strength, functional significance and origins of direct parasympathetic innervation of the left ventricle (LV) remain controversial. In the present study we used an anaesthetized rat model to first confirm the presence of tonic inhibitory vagal influence on LV inotropy. Using genetic neuronal targeting and functional neuroanatomical mapping we tested the hypothesis that parasympathetic control of LV contractility is provided by vagal preganglionic neurones located in the dorsal motor nucleus (DVMN). It was found that under systemic β-adrenoceptor blockade (atenolol) combined with spinal cord (C1) transection (to remove sympathetic influences), intravenous administration of atropine increases LV contractility in rats anaesthetized with urethane, but not in animals anaesthetized with pentobarbital. Increased LV contractility in rats anaesthetized with urethane was also observed when DVMN neurones targeted bilaterally to express an inhibitory Drosophila allatostatin receptor were silenced by application of an insect peptide allatostatin. Microinjections of glutamate and muscimol to activate or inhibit neuronal cell bodies in distinct locations along the rostro-caudal extent of the left and right DVMN revealed that vagal preganglionic neurones, which have an impact on LV contractility, are located in the caudal region of the left DVMN. Changes in LV contractility were only observed when this subpopulation of DVMN neurones was activated or inhibited. These data confirm the existence of a tonic inhibitory muscarinic influence on LV contractility. Activity of a subpopulation of DVMN neurones provides functionally significant parasympathetic control of LV contractile function.
authors.affiliation: Centre for Cardiovascular and Metabolic Neuroscience, Neuroscience, Physiology and Pharmacology, University College London, London, WC1E 6BT, UK.|UCL Centre for Advanced Biomedical Imaging, Division of Medicine, University College London, London, WC1E 6DD, UK.
authors.forename: Asif
authors.initials: A
authors.lastname: Machhada
authors.affiliation: Centre for Cardiovascular and Metabolic Neuroscience, Neuroscience, Physiology and Pharmacology, University College London, London, WC1E 6BT, UK.
authors.forename: Nephtali
authors.initials: N
authors.lastname: Marina
authors.affiliation: Centre for Cardiovascular and Metabolic Neuroscience, Neuroscience, Physiology and Pharmacology, University College London, London, WC1E 6BT, UK.
authors.forename: Alla
authors.initials: A
authors.lastname: Korsak
authors.affiliation: UCL Centre for Advanced Biomedical Imaging, Division of Medicine, University College London, London, WC1E 6DD, UK.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Stuckey
authors.affiliation: UCL Centre for Advanced Biomedical Imaging, Division of Medicine, University College London, London, WC1E 6DD, UK.
authors.forename: Mark F
authors.initials: MF
authors.lastname: Lythgoe
authors.affiliation: Centre for Cardiovascular and Metabolic Neuroscience, Neuroscience, Physiology and Pharmacology, University College London, London, WC1E 6BT, UK.
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Gourine
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D058785:GABA-A Receptor Agonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000187:drug effects; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009118:Muscimol / Q000494:pharmacology; D009200:Myocardial Contraction / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009479:Neuropeptides / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D014463:Ultrasonography; D014630:Vagus Nerve / Q000502:physiology*; D016276:Ventricular Function / Q000187:drug effects
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D058785:GABA-A Receptor Agonists; D018727:Muscarinic Antagonists; D009479:Neuropeptides; C076523:allatostatin; D009118:Muscimol; D018698:Glutamic Acid; D001262:Atenolol; D001285:Atropine