Plasma angiotensins under sustained converting enzyme inhibition with enalapril in normal humans

During converting enzyme inhibition, a striking difference is found between plasma immunoreactive angiotensin (ANG) II and ANG-(1-8)octapeptide as specifically measured after high performance liquid chromatography (HPLC). The relative contributions to this difference of cross-reacting ANG I and shorter ANG peptides other than (1-8)octapeptide are not known. Eight normal volunteers were given a daily single oral dose of enalapril (20 mg) for 4 days. Plasma levels of ANG-(1-8)octapeptide, (2-8)heptapeptide, (3-8)hexapeptide and (4-8)pentapeptide as well as blood concentrations of ANG I and plasma angiotensin converting enzyme activity were measured before and 4 h post drug on the first and the last day of treatment. Plasma peptides were extracted with bonded-phase silica and separated by isocratic reversed-phase HPLC before radio-immunoassay. Significant cross-reactivity of an antiserum permitted the individual measurement of different ANG peptides and metabolites in plasma. During converting enzyme inhibition, the plasma levels of ANG metabolites tended to decrease, but they remained measurable. Thus, depending on the specificity of the antiserum used, conventional measurement of immunoreactive ANG II underestimates to various degrees the inhibition of angiotensin converting enzyme.