Muscarinic receptor agonists and antagonists: effects on cardiovascular function

Handb Exp Pharmacol. 2012:(208):299-316. doi: 10.1007/978-3-642-23274-9_13.

Abstract

Muscarinic receptor activation plays an essential role in parasympathetic regulation of cardiovascular function. The primary effect of parasympathetic stimulation is to decrease cardiac output by inhibiting heart rate. However, pharmacologically, muscarinic agonists are actually capable of producing both inhibitory and stimulatory effects on the heart as well as vasculature. This reflects the fact that muscarinic receptors are expressed throughout the cardiovascular system, even though they are not always involved in mediating parasympathetic responses. In the heart, in addition to regulating heart rate by altering the electrical activity of the sinoatrial node, activation of M₂ receptors can affect conduction of electrical impulses through the atrioventricular node. These same receptors can also regulate the electrical and mechanical activity of the atria and ventricles. In the vasculature, activation of M₃ and M₅ receptors in epithelial cells can cause vasorelaxation, while activation of M₁ or M₃ receptors in vascular smooth muscle cells can cause vasoconstriction in the absence of endothelium. This review focuses on our current understanding of the signaling mechanisms involved in mediating these responses.

Publication types

  • Review

MeSH terms

  • Acetylcholine / metabolism
  • Animals
  • Cardiovascular Agents / pharmacology*
  • Cardiovascular Diseases / drug therapy
  • Cardiovascular Diseases / metabolism
  • Cardiovascular Diseases / physiopathology
  • Cardiovascular System / drug effects*
  • Cardiovascular System / innervation
  • Cardiovascular System / metabolism
  • Humans
  • Muscarinic Agonists / pharmacology*
  • Muscarinic Antagonists / pharmacology*
  • Parasympathetic Nervous System / drug effects*
  • Parasympathetic Nervous System / metabolism
  • Parasympathetic Nervous System / physiopathology
  • Receptors, Muscarinic / drug effects*
  • Receptors, Muscarinic / metabolism
  • Signal Transduction / drug effects

Substances

  • Cardiovascular Agents
  • Muscarinic Agonists
  • Muscarinic Antagonists
  • Receptors, Muscarinic
  • Acetylcholine