After single or multiple administration of an angiotensin converting enzyme(ACE) inhibitor, plasma angiotensin(ANG) II recovers more rapidly than plasma ACE-activity. To investigate the dynamics of ...the biochemical changes induced by ACE inhibition, 6 normal volunteers received in a randomized order one dose of enalapril (E, 20mg), an ACE-inhibitor with a 35 hour terminal half-life, or benazepril (B, 20 mg), an ACE-inhibitor with a 23 hour terminal half-life. Biochemical effects of the 2 agents were compared at 0-4 hours and 14-30 hours after drug intake. ACE-inhibition was estimated in vivc by the ratio between plasma ANG II and blood ANG I (ANG II/ANG I) and in vitro by a radioenzymatic assay. At peak inhibition (4 hours after E, 2 hours after B), plasma ACE-activity was inhibited with E by 94% in vivo and by 98% in vitro, compared to 98% and 97%, respectively, with B. Twenty-four hours post drug, plasma ACE-activity was inhibited with E by 84% in vivo and by 83% in vitro, compared to 64% and 94%, respectively, with B. Plasma ACE-inhibition largely exceeded 24 hours and was independent of terminal half-lives. ANG II levels were initially suppressed by 88% with E and by 95% with B, but they returned to their initial values within 24 hours. Active renin measured by IRMA was increased to 183% and 313% 4 and 24 hours after E, and to 342% and 337% after B. Corresponding ANG I levels were 240% and 319% for E, and 329% and 295% for B; they were highly correlated to active renin (r=0.82, n=252, p<0.001). Thus, 24 hours post-drug, ANG II/ANG I was still reduced but the biologically effective product of the renin-angiotensin system(RAS), ANG II, has returned to its initial level, as a consequence of the increase in renin secretion and ANG I production. The RAS is reset at a time when ACE-inhibition is still effective. Feed-back increase in renin release seems to be an important factor contributing to the reappearance of ANG II in plasma in the presence of ACE-inhibition.
