ALTERATIONS OF METHIONINE FLUXES AND INCORPORATION IN INTESTINES OF MINIATURE PIGS FED A DIET HIGH IN CASEINATE ARE RESTRICTED BY ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR

Previous results from our laboratory showed that a methionine-rich cas einate-based (metcas) diet induces hyperhomocysteinemia in miniature p igs. In the present study, the contribution of the ileal and jejunal m ethionine absorption to the dietary induced hyperhomocysteinemia was e valuated by measuring the mucosal to serosal fluxes and the enterocyte incorporation in intact intestinal epithelia mounted in Ussing chambe rs. For 4 mo, 20 miniature pigs were daily fed control or metcas diets , and an oral combination of an angiotensin-converting enzyme inhibito r (25 mg captopril, Cp) and diuretic (12.5 mg hydrochlorothiazide, HTZ ) or placebo. Ileal methionine fluxes were lower, and jejunal methioni ne incorporation was higher in epithelia from miniature pigs fed metca s than in that from other groups. For a given transepithelial flux of methionine, i.e., a constant amount of methionine recovered in the ser osal chamber, a greater enterocyte incorporation was detected. Cp-HTZ treatment corrected the diet-induced methionine trapping in intestinal epithelia but had little effect in control animals. In separate in vi tro experiments, Cp added alone significantly activated methionine flu xes in epithelia from metcas-fed miniature pigs as it did in vivo, dem onstrating that Cp rather than HTZ mainly contributed to the in vivo e ffects of the drug combination. Our results showed that the regulation of intestinal methionine absorption compensated the diet-induced hype rhomocysteinemia and that Cp-HTZ treatment altered these adaptative ch anges without increasing methioninemia and homocysteinemia.