Regulation of angiotensin converting enzyme.
Angiotensin converting enzyme (ACE;EC 3.4.15.1), or kininase II, was studied in serum, cultured endothelial cells from cord artery, in macrophages of humans, and in serum and purified plasma membranes of rats following treatment with inducers of ACE biosynthesis. ACE activity was measured in biological fluids with an enzyme kinetic method employing synthetic 1-hipp-1-his-l-leu tripeptide as a substrate, and with a new method using 125I-labelled specific inhibitor of ACE as a sensitive probe for ACE binding sites. The latter technique also proved suitable for the quantification of ACE in cells. Anti-human ACE antibody was employed for immunofluorescence studies in human cells. Dexamethasone treatment caused an increase in ACE in cultured human endothelial cells, macrophages and in rat pulmonary plasma membranes, but failed to increase serum ACE activity in rats. Captopril and enalapril treatment of hypertensive patients increased total serum ACE, the increase being evident after removal of the active drug from the serum by prolonged storage or chloramine T treatment (captopril) or by dialysis (enalapril). Captopril increased the ACE content of endothelial cells and macrophages. Macrophages appeared sensitive to captopril induction of ACE biosynthesis after pre-stimulation with Escherichia coli lipopolysaccharide. Dexamethasone treatment potentiated the known induction of ACE in rat pulmonary tissue. Thus ACE biosynthesis may be enhanced by three categories of treatment: (1) glucocorticoid; (2) macrophage activation; (3) ACE inhibitors. The precise mechanism of ACE induction and its possible biological relevance await further clarification.
D000328:Adult; D000818:Animals; D002216:Captopril / Q000627:therapeutic use; D004656:Enalapril / Q000627:therapeutic use; D004727:Endothelium / Q000201:enzymology; D005260:Female; D006333:Heart Failure / Q000188:drug therapy / Q000201:enzymology*; D006801:Humans; D006978:Hypertension, Renovascular / Q000188:drug therapy / Q000201:enzymology*; D007700:Kinetics; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D014469:Umbilical Arteries / Q000201:enzymology
D004656:Enalapril; D002216:Captopril; D007703:Peptidyl-Dipeptidase A