ANGIOTENSIN AND BRADYKININ METABOLISM BY PEPTIDASES IDENTIFIED IN CULTURED HUMAN SKELETAL-MUSCLE MYOCYTES AND FIBROBLASTS

Angiotensin (ANG) and kinin metabolizing enzymes, angiotensin-converti ng enzyme (ACE; EC 3.4.15.1), neutral endopeptidase-24.11 (NEP-24.11;E C 3.4.24.11), and aminopeptidase M (AmM; EC 3.4.11.2), have recently b een identified in a purified skeletal muscle glycoprotein fraction. We have analyzed the cellular localization of these enzymes. In cultured human skeletal muscle adult myoblasts, myotubes, and fibroblasts, kin ins and angiotensins were metabolized by NEP-24.11 and AmM but not by ACE. NEP-24.11 degraded ANG II, ANG III, and bradykinin (BK) and conve rted ANG I to the active metabolite ANG(1-7). ANG III was converted to the novel ANG IV metabolite [des-Arg(1)]ANG III by AmM. These data su ggest that, due to their abundance in the body, skeletal muscle myocyt es and fibroblasts may play a major role in modulation of the systemic and local effects of angiotensins and kinins. This role could be part icularly important in individuals receiving treatment with ACE inhibit ors.