Inhibition of rabbit lung angiotensin converting enzyme by idrapril

Abstract

Idrapril, the prototype of a new class of angiotensin converting enzyme (ACE) inhibitors, competitively inhibited, with nanomolar apparent K i the hydrolysis of hippuryl-glycyl-glycine by rabbit lung ACE. The pre-steady-state analysis of this tight-binding inhibition showed it to be characterized by slow kinetics, but at variance with what was found for enalaprilat in the same conditions, idrapril appeared to act through a simple, single step mechanism. Kinetic K i and K on and k off values were 470 pM, 3.0 ± 1.5 × 10 6 M −1sec −1 and 1.4±0.3 × 10 −3sec −1, respectively.