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Human intestinal brush border angiotensin-converting enzyme activity and its inhibition by antihypertensive Ramipril

1988; Elsevier BV; Volume: 94; Issue: 4 Linguagem: Inglês

10.1016/0016-5085(88)90551-3

1528-0012

Bruce R. Stevens, Alarico Fernandez, Christine Kneer, J J Cerda, M. Ian Phillips, Edward R. Woodward,

Enzyme function and inhibition

Angiotensin-converting enzyme (ACE) has been identified as a prominent brush border membranebound enzyme of human jejunum.In this study, we purified brush border membrane vesicles enriched in ACE, and characterized the ACE with regard to (a) its stability in the membrane, (b) substrate hydrolysis kinetics compared with pulmonary endothelial ACE, and (c) pharmacologic interaction with Ramipril.These investigations resulted in the following findings.The uninhibited enzyme is stable in native membranes in vitro, with a half-life of 195 * 7 h.Kinetic analysis of ACE hydrolysis activity revealed the presence of a single enzyme species, which yielded a high V,, and displayed a K,,, similar to purified ACE from lung endothelium.Brush border ACE was inhibited by Ramipril, one of the most specific and potent orally administered ACE inhibitors indicated for hypertension.We determined the brush border ACE value of I& = 3 x lo-' M Ramipril-diacid, which is the same value for serum and lung ACE.Brush border ACE remains 100% inhibited by 10 PM Ramipril during at least 8 days in vitro.The data indicate that ACE is a prominent jejunal brush border enzyme that behaves pharmacologically and kinetically like its peripheral circulation counterpart.This study suggests that high doses of orally administered ACE inhibitors may affect intestinal epithelial function.(8-111, can completely inhibit intestinal ACE in vitro.