Mechanisms of altered vagal control in heart failure: Influence of muscarinic receptors and acetylcholinesterase activity

Mark E. Dunlap, Steve Bibevski, Terrone L. Rosenberry, Paul Ernsberger

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

Parasympathetic control of the heart is attenuated in heart failure (HF). We investigated possible mechanisms and sites of altered vagal control in dogs with HF induced by rapid pacing. Muscarinic blockade reduced the R-R interval by 308 ms in controls but only by 32 ms in HF, indicating low levels of resting vagal tone. Vagomimetic doses of atropine sulfate prolonged the R-R interval by 109 ms in controls and increased standard deviation of the R-R interval by 66 ms but only by 46 and 16 ms, respectively, in HF. Bradycardia elicited by electrical stimulation of the vagus nerve was also attenuated in the HF group. Conversely, muscarinic receptor activation by bethanechol, and indirectly by neostigmine, elicited exaggerated R-R interval responses in HF. To investigate possible mechanisms, we measured muscarinic receptor density (Bmax) and acetylcholinesterase activity in different areas of the heart. In sinoatrial nodes, Bmax was increased (230 ± 75% of control) and acetylcholinesterase decreased (80 ± 6% of control) in HF. We conclude that muscarinic receptors are upregulated and acetylcholinesterase is reduced in the sinus node in HF. Therefore, reduced vagal control in HF is most likely due to changes of presynaptic function (ganglionic), because postsynaptic mechanisms augment vagal control in HF.

Original languageEnglish (US)
Pages (from-to)H1632-H1640
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume285
Issue number4 54-4
DOIs
StatePublished - Oct 1 2003

Keywords

  • Autonomic
  • Cholinergic
  • Parasympathetic

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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