Novel approaches to restore parasympathetic activity to the heart in cardiorespiratory diseases

Am J Physiol Heart Circ Physiol. 2020 Dec 1;319(6):H1153-H1161. doi: 10.1152/ajpheart.00398.2020. Epub 2020 Oct 9.

Abstract

Neural control of the heart is regulated by sympathetic and parasympathetic divisions of the autonomic nervous system, both opposing each other to maintain cardiac homeostasis via regulating heart rate, conduction velocity, force of contraction, and coronary blood flow. Sympathetic hyperactivity and diminished parasympathetic activity are the characteristic features of many cardiovascular disease states including hypertension, myocardial ischemia, and arrhythmias that result in heart failure. Restoring parasympathetic activity to the heart has recently been identified as the promising approach to treat such conditions. However, approaches that used vagal nerve stimulation have been shown to be unsuccessful in heart failure. This review focuses on novel chemogenetic approaches used to identify the cardioprotective nature of activating neural points along the vagal pathway (both central and peripheral) while being selectively therapeutic in heart failure and obstructive sleep apnea.

Keywords: chemogenetic; cholinergic; oxytocin; parasympathetic; vagus.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Choline O-Acetyltransferase / genetics
  • Choline O-Acetyltransferase / metabolism*
  • Enzyme Activators / therapeutic use*
  • Heart / innervation*
  • Heart Failure / drug therapy*
  • Heart Failure / genetics
  • Heart Failure / metabolism
  • Heart Failure / physiopathology
  • Hemodynamics / drug effects
  • Humans
  • Ligands
  • Muscarinic Agonists / therapeutic use*
  • Oxytocin / metabolism
  • Receptors, Muscarinic / drug effects*
  • Receptors, Muscarinic / genetics
  • Receptors, Muscarinic / metabolism
  • Sleep Apnea, Obstructive / drug therapy*
  • Sleep Apnea, Obstructive / genetics
  • Sleep Apnea, Obstructive / metabolism
  • Sleep Apnea, Obstructive / physiopathology
  • Vagus Nerve / drug effects*
  • Vagus Nerve / metabolism
  • Vagus Nerve / physiopathology

Substances

  • Enzyme Activators
  • Ligands
  • Muscarinic Agonists
  • Receptors, Muscarinic
  • Oxytocin
  • Choline O-Acetyltransferase