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Deoxycholyltaurine-induced vasodilation of rodent aorta is nitric oxide- and muscarinic M(3) receptor-dependent.
- Source :
-
European journal of pharmacology [Eur J Pharmacol] 2005 Jul 04; Vol. 517 (1-2), pp. 103-10. - Publication Year :
- 2005
-
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 microM 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 microM 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 M(3) receptor knockout. We conclude that the systemic vasodilatory actions of deoxycholyltaurine are mediated in part by a nitric oxide-, muscarinic M(3) 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.
- Subjects :
- Acetylcholine pharmacology
Adenosine Triphosphate pharmacology
Animals
Aorta, Thoracic physiology
Bile Acids and Salts pharmacology
Dose-Response Relationship, Drug
Endothelium, Vascular physiology
Enzyme Inhibitors pharmacology
Female
Genotype
In Vitro Techniques
Lithocholic Acid analogs & derivatives
Lithocholic Acid pharmacology
Male
Mice
Mice, Inbred Strains
Mice, Knockout
Molsidomine analogs & derivatives
Molsidomine pharmacology
NG-Nitroarginine Methyl Ester pharmacology
Nitric Oxide Donors pharmacology
Nitric Oxide Synthase antagonists & inhibitors
Nitroarginine pharmacology
Phenylephrine pharmacology
Rats
Rats, Sprague-Dawley
Receptor, Muscarinic M3 antagonists & inhibitors
Receptor, Muscarinic M3 genetics
Vasoconstrictor Agents pharmacology
Vasodilator Agents pharmacology
Aorta, Thoracic drug effects
Nitric Oxide physiology
Receptor, Muscarinic M3 physiology
Taurodeoxycholic Acid pharmacology
Vasodilation drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 0014-2999
- Volume :
- 517
- Issue :
- 1-2
- Database :
- MEDLINE
- Journal :
- European journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 15964566
- Full Text :
- https://doi.org/10.1016/j.ejphar.2005.05.037