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

摘要

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.