Deoxycholyltaurine-induced vasodilation of rodent aorta is nitric oxide- and muscarinic M3 receptor-dependent

Sandeep Khurana, Masahisa Yamada, Jürgen Wess, Richard H. Kennedy, Jean Pierre Raufman

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Emerging evidence indicates that some secondary bile acids interact functionally with muscarinic cholinergic receptors. Using thoracic aortic rings prepared from rats and mice, we examined the mechanism of deoxycholyltaurine- induced vasorelaxation. Increasing concentrations of both acetylcholine (1 nM to 0.1 mM) and deoxycholyltaurine (0.1 μM to 1 mM) stimulated relaxation of phenylephrine-constricted rings prepared from rat thoracic aortae. These effects were reduced by endothelial denudation and by treatment with an inhibitor of nitric oxide formation and with a synthetic acetylcholine: bile acid hybrid that acts as a muscarinic receptor antagonist. Likewise, both acetylcholine (1 nM to 0.1 mM) and deoxycholyltaurine (0.1 μM to 0.1 mM) stimulated relaxation of phenylephrine-constricted rings prepared from mouse thoracic aortae. These effects were reduced by endothelial denudation, addition of an inhibitor of nitric oxide formation, and by muscarinic M3 receptor knockout. We conclude that the systemic vasodilatory actions of deoxycholyltaurine are mediated in part by a nitric oxide-, muscarinic M3 receptor-dependent mechanism. In advanced liver disease, interaction of serum bile acids with endothelial muscarinic receptors may explain nitric oxide overproduction in the systemic circulation and resulting peripheral arterial vasodilation.

Original languageEnglish (US)
Pages (from-to)103-110
Number of pages8
JournalEuropean Journal of Pharmacology
Volume517
Issue number1-2
DOIs
StatePublished - Jul 4 2005

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Taurodeoxycholic Acid
Muscarinic M3 Receptors
Vasodilation
Aorta
Rodentia
Nitric Oxide
Muscarinic Receptors
Bile Acids and Salts
Acetylcholine
Phenylephrine
Thoracic Aorta
Muscarinic Antagonists
Cholinergic Receptors
Liver Diseases
Thorax
Serum

Keywords

  • Cholinergic receptor
  • Cirrhosis
  • Deoxycholic acid
  • Receptor subtype
  • Vascular relaxation

ASJC Scopus subject areas

  • Pharmacology

Cite this

Deoxycholyltaurine-induced vasodilation of rodent aorta is nitric oxide- and muscarinic M3 receptor-dependent. / Khurana, Sandeep; Yamada, Masahisa; Wess, Jürgen; Kennedy, Richard H.; Raufman, Jean Pierre.

In: European Journal of Pharmacology, Vol. 517, No. 1-2, 04.07.2005, p. 103-110.

Research output: Contribution to journalArticle

Khurana, Sandeep ; Yamada, Masahisa ; Wess, Jürgen ; Kennedy, Richard H. ; Raufman, Jean Pierre. / Deoxycholyltaurine-induced vasodilation of rodent aorta is nitric oxide- and muscarinic M3 receptor-dependent. In: European Journal of Pharmacology. 2005 ; Vol. 517, No. 1-2. pp. 103-110.
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