Angiotensin Converting Enzyme Activity in Human Serum: Relationship to Enzyme Inhibitor In Vivo and In Vitro

Abstract

Quantitative relationships between angiotensin converting enzyme activity in human serum and concentration of an enzyme inhibitor, the active diacid metabolite of MK-421 [N-(S-1-carbethoxy-3-phenylpropyl)-S-alanyl-S-proline maleate], were defined. Dose-response curves were generated in vitro by adding the diacid metabolite (DM) to serum (ID50 = to 6x10-9 M); l0-15% of initial activity was nonsuppressible. DM an converting enzyme activity were also measured in serum from hypertensive subjects receiving oral MK-421. The dose-response curve for serum samples following single doses of MK-421 (ID50 = 6x10-9M), was similar to curves generated in vitro while the curve for sample following chronic therapy suggested a small decrease in inhibitory potency.