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On the in vitro vasoactivity of bile acids
Article first published online: 29 JAN 2009
DOI: 10.1038/sj.bjp.0703554
2000 British Pharmacological Society
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How to Cite
Ljubuncic, P., Said, O., Ehrlich, Y., Meddings, J. B., Shaffer, E. A. and Bomzon, A. (2000), On the in vitro vasoactivity of bile acids. British Journal of Pharmacology, 131: 387–398. doi: 10.1038/sj.bjp.0703554
Publication History
- Issue published online: 29 JAN 2009
- Article first published online: 29 JAN 2009
- (Received May 5, 2000, Accepted June 23, 2000)
- Abstract
- Article
- References
- Cited By
Keywords:
- Bile acids;
- vascular reactivity;
- α1-adrenoceptors;
- endothelium;
- nitric oxide;
- prostacyclin;
- L-NAME, indomethacin, hydrophobic–hydrophilic balance, vasorelaxation
We compared the vasorelaxant action of nine different bile acids and correlated their vasorelaxant activity with their individual indices for hydrophobicity or lipophilicity.
Vasorelaxant activity correlated with the relative lipid solubility of bile acids with lipophilic bile acids exhibiting the greatest vasorelaxant activity with modest to no vasorelaxant activity exhibited by hydrophilic bile acids.
We also investigated whether bile acid-induced vasorelaxation is mediated by antagonism of a prototypal contractile receptor, the α1-adrenoceptor, by stimulation of a bile acid surface membrane receptor, by the release of endothelium-derived relaxant factors, by promoting the generation of reactive oxygen species and increasing the extent of lipid peroxidation, or by modifying membrane fluidity.
Lipophilic bile acids induce vasorelaxation possibly by antagonizing α1-adrenoceptors, a phenomenon that manifests itself as a lowering of the affinity of vascular α1-adrenoceptors. Bile acid-induced vasorelaxation was not dependent upon stimulation of a bile acid surface membrane receptor or the release of endothelium-derived relaxant factors.
Lipophilic bile acids can also increase the extent of lipid peroxidation with a subtle reduction in the fluidity of rat vascular smooth muscle membranes not associated with loss of membrane cholesterol or phospholipid.
We have concluded that lipophilic bile acids are non-selective vasorelaxants whose mechanism of action is a multifaceted process involving antagonism of contractile surface membrane receptors possibly effected by an increased extent of lipid peroxidation and/or membrane fluidity but occurs independent of the release of endothelial-derived relaxant factors or stimulation of a surface membrane bile acid binding site.
British Journal of Pharmacology (2000) 131, 387–398; doi:10.1038/sj.bjp.0703554