The Induction of Angiotensin Converting enzyme by Its Inhibitors

The inhibitors of angiotensin converting enzyme (ACE), captopril and enalapril, were found to increase ACE concentration in cultured human endothelial cells from cord artery as measured with a novel ACE assay employing MK 351A, an inhibitor of ACE, and with immunofluorescense labeling using anti-human lung ACE antibody. Dexamethasone (10 nM) also increased ACE and potentiated the increase of cellular ACE caused by captopril. Similar effects of ACE inhibitors were seen in cultured human macrophages, particularly after prestimulation with E. coli lipopolysaccharide. In Wistar Kyoto rats, captopril caused a 3-fold increase of serum ACE, while dexamethasone (40 ug/day, 14 days) did not increase serum ACE. Combined treatment with captopril and dexamethasone caused a 5-fold increase of ACE in purified lung plasma membranes. ACE inhibitors induce increased ACE biosynthesis in endothelial cells, and in macrophages. The rise of cellular ACE with ACE inhibitors is potentiated by glucocorticoid.