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 caseinate-based (metcas) diet induces hyperhomocysteinemia in miniature pigs. In the present study, the contribution of the ileal and jejunal methionine absorption to the dietary induced hyperhomocysteinemia was evaluated by measuring the mucosal to serosal fluxes and the enterocyte incorporation in intact intestinal epithelia mounted in Ussing chambers. For 4 mo, 20 miniature pigs were daily fed control or metcas diets, and an oral combination of an angiotensin-converting enzyme inhibitor (25 mg captopril, Cp) and diuretic (12.5 mg hydrochlorothiazide, HTZ) or placebo. Ileal methionine fluxes were lower, and jejunal methionine incorporation was higher in epithelia from miniature pigs fed metcas than in that from other groups. For a given transepithelial flux of methionine, i.e., a constant amount of methionine recovered in the serosal 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 vitro experiments, Cp added alone significantly activated methionine fluxes in epithelia from metcas-fed miniature pigs as it did in vivo, demonstrating that Cp rather than HTZ mainly contributed to the in vivo effects of the drug combination. Our results showed that the regulation of intestinal methionine absorption compensated the diet-induced hyperhomocysteinemia and that Cp-HTZ treatment altered these adaptative changes without increasing methioninemia and homocysteinemia. INDEXING KEY WORDS: miniature pig; intestinal absorption; methionine; hyperhomocysteinemia; ACE inhibition