Glucocorticoid induction of angiotensin converting enzyme production from bovine endothelial cells in culture and rat lung in vivo.
1. Endothelial cells from bovine aortae, grown to confluence in culture and then maintained for 2 days in serum-free medium produced an enzyme which closely resembled angiotensin converting enzyme (ACE). 2. Dexamethasone increased cell ACE activity 6- to 7-fold with a threshold near 0.3 nmol/l. This effect was completely inhibited by actinomycin D or cycloheximide. 3. Deoxycorticosterone (DOC) and aldosterone were approximately 0.1% as active as dexamethasone. 4. In cells incubated in the presence of dexamethasone (10 nmol/l), DOC (10 mumol/l) inhibited ACE production suggesting that DOC is a partial glucocorticoid agonist/antagonist in this system. 5. Adrenalectomized rats had lower pulmonary ACE compared to intact controls. This was restored by injections of dexamethasone (40 micrograms/day) but not by DOC (40 micrograms/day) or aldosterone (10 micrograms/day). The dose response curve for dexamethasone induction of pulmonary ACE mirrored that for thymolysis; for both, half maximal effects were seen at approximately equal to 6 micrograms/day and plateau levels at approximately equal to 60 micrograms/day. 6. Glucocorticoids appear to be potent inducers of ACE activity in endothelial cells in culture and rat lung in vivo. The action of DOC and aldosterone probably reflects occupancy of glucocorticoid receptors. This effect may be of significance in modulating ACE in local vascular beds.
D000818:Animals; D001808:Blood Vessels / Q000201:enzymology*; D002417:Cattle; D002478:Cells, Cultured; D004727:Endothelium / Q000201:enzymology; D004790:Enzyme Induction; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D008168:Lung / Q000201:enzymology*; D007703:Peptidyl-Dipeptidase A / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains
D005938:Glucocorticoids; D007703:Peptidyl-Dipeptidase A