Need for plasma angiotensin measurements to investigate converting-enzyme inhibition in humans

Since only a minute proportion of total angiotensin-converting enzyme (ACE) is present in plasma, the reliability of conventional in vitro measurements of ACE activity has been questioned. Data presented here demonstrate that the definition of ACE inhibition depends on the methodology used, with different results obtained with different substrates. We have developed a method that provides accurate and precise determinations of "true" angiotensin levels and in vivo ACE activity was estimated by measuring the plasma angiotensin II/angiotensin I ratio. Since the initial interruption of angiotensin II production by an ACE inhibitor stimulates renal renin release, the response can be quantitated by measuring changes in plasma levels of angiotensin I. The actual state of the renin-angiotensin system during ACE inhibition is represented by the plasma angiotensin II level. When ACE inhibition is no longer complete, increased angiotensin I levels bring the system back toward initial angiotensin II concentrations.