ABNORMAL TAUROCHOLATE ILEAL TRANSEPITHELIAL TRANSPORT IN ATHEROSCLEROTIC MINIPIGS AND EFFECTS OF ACE-INHIBITORS

In atherosclerotic mini-pigs, we attempted to determine (i) whether hi gh-fat atherogenic diet disturbs the taurocholate transepithelial tran sport and incorporation in the ileal epithelium mounted in Ussing cham bers, and (ii) whether these processes are sensitive to angiotensin co nverting enzyme (ACE) inhibitors which slow the development of vascula r atherosclerosis, In atherosclerotic mini-pigs, the mucosal to serosa l transepithelial fluxes were markedly lower (72%, inhibition) and fre e diffusion was more altered than active processes. Taurocholate incor poration into enterocyte (75%, inhibition) paralleled the flux reducti on. The transport disturbance observed here might be explained by chan ges in bile salt permeability in relation to alterations of the membra ne properties. Taurocholate absorption was lowered by atherogenic diet , whereas bile salts were not trapped in the enterocyte, therefore ath erosclerosis-induced alterations preferentially affected the passage t hrough the brush-border. In the ACE inhibitor treated atherosclerotic mini-pigs, perindopril and enalapril similarly inhibited serum ACE act ivities. Perindopril further corrected taurocholate fluxes by 50%, and fully restored taurocholate incorporation. Since enalapril did not re store the atherosclerosis-induced alterations, the involvement of inte stinal ACE in bile acid recycling and of an ACE inhibitor class effect on these mechanisms both remain to be ascertained.