Orally administered angiotensin-converting enzyme-inhibitors captopril and isoleucine-proline-proline have distinct effects on local renin-angiotensin system and corticosterone synthesis in dextran sulfate sodium-induced colitis in mice

The effects of angiotensin-converting enzyme (ace) inhibition by an antihypertensive drug,captopril,and milk casein-derived ace-inhibiting bioactive tripeptide isoleucine-proline-proline (ile-pro-pro),on local renin-angiotensin system (ras) and glucocorticoid production in the intestine were studied in the dextran sodium sulfate induced colitis in mice. mice received water or 3% dextran sodium sulfate with or without either 15.7 mg/l captopril or 833 mg/l ile-pro-pro for 7 days. captopril and ile-pro-pro were found to have distinct effects on local renin-angiotensin system and mrna expression of glucocorticoid synthesis components in colon in vitro. captopril reduced intestinal mrna expression of angiotensin-converting enzyme,angiotensinogen and cyp11b1,whereas ile-pro-pro reduced angiotensin-converting enzyme protein shedding from colon. neither captopril nor ile-pro-pro changed the expression of glucocorticoid-synthesis driving transcription factor lrh-1 expression or intestinal glucocorticoid production. contrary to previous studies,captopril did not alleviate dss-induced colitis. furthermore,ile-pro-pro was mildly pro-inflammatory as exhibited by increased pro-inflammatory cytokine interleukin-1β (il-1β) and tumor necrosis factor-α (tnf-α) levels in colon. the nutritional component ile-pro-pro had different effect on intestinal ras and glucocorticoid (gc) synthesis pathway than ace inhibitor captopril,which suggests that the bioactivity of ile-pro-pro is not limited to inhibition of ace. © 2017,polish physiological society. all rights reserved.