APP and angioedema: When drug therapy inhibits ACE, the secondary bradykinin metabolic enzymes (APP, kininase I, NEP, and DPP-4) assume a relatively larger role in degrading bradykinin, des-Arg9-BK, and substance P. Thus, defects or deficiencies of these enzymes theoretically predispose patients to developing angioedema when taking an ACE inhibitor.