Abnormal taurocholate ileal transepithelial transport in atherosclerotic mini-pigs and effects of ACE inhibitors.
In atherosclerotic mini-pigs, we attempted to determine (i) whether high-fat atherogenic diet disturbs the taurocholate transepithelial transport and incorporation in the ileal epithelium mounted in Ussing chambers, and (ii) whether these processes are sensitive to angiotensin converting enzyme (ACE) inhibitors which slow the development of vascular atherosclerosis. In atherosclerotic mini-pigs, the mucosal to serosal transepithelial fluxes were markedly lower (72% inhibition) and free diffusion was more altered than active processes. Taurocholate incorporation into enterocyte (75% inhibition) paralleled the flux reduction. The transport disturbance observed here might be explained by changes in bile salt permeability in relation to alterations of the membrane properties. Taurocholate absorption was lowered by atherogenic diet, whereas bile salts were not trapped in the enterocyte, therefore atherosclerosis-induced alterations preferentially affected the passage through the brush-border. In the ACE inhibitor treated atherosclerotic mini-pigs, perindopril and enalapril similarly inhibited serum ACE activities. Perindopril further corrected taurocholate fluxes by 50% and fully restored taurocholate incorporation. Since enalapril did not restore the atherosclerosis-induced alterations, the involvement of intestinal ACE in bile acid recycling and of an ACE inhibitor class effect on these mechanisms both remain to be ascertained.
Rahmani-Jourdheuil
D
D
INSERM CJF 9401, Faculté de Pharmacie, Marseille, France.
Masset
D
D
Rolland
P H
PH
Garçon
D
D
Rahmani
R
R
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001161:Arteriosclerosis / Q000097:blood / Q000378:metabolism*; D001692:Biological Transport; D004656:Enalapril / Q000494:pharmacology; D004848:Epithelium / Q000378:metabolism; D007082:Ileum / Q000378:metabolism*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism; D008055:Lipids / Q000097:blood; D020913:Perindopril; D013552:Swine; D013556:Swine, Miniature; D013656:Taurocholic Acid / Q000378:metabolism*
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; D008055:Lipids; D013656:Taurocholic Acid; D004656:Enalapril; D020913:Perindopril