Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1982 Sep;70(3):684–692. doi: 10.1172/JCI110663

Induction by Glucocorticoids of Angiotensin Converting Enzyme Production from Bovine Endothelial Cells in Culture and Rat Lung In Vivo

F A O Mendelsohn 1,2,3, C J Lloyd 1,2,3, C Kachel 1,2,3, J W Funder 1,2,3
PMCID: PMC370272  PMID: 6286730

Abstract

The effect of corticosteroids on angiotensin converting enzyme was investigated in endothelial cell cultures and intact rat lung. Cultured endothelial cells from bovine aorta showed net production of angiotensin converting enzyme (ACE) over 2 d culture in serum-free medium. Dexamethasone (DM) increased cell ACE activity six- to sevenfold at 100 nM with a threshold effect at 0.3 nM. The effect of DM on ACE production was completely inhibited by actinomycin D or cycloheximide. Deoxycorticosterone (DOC) and aldosterone were markedly less active, with a threshold near 100 nM and significant (two to threefold) stimulation of ACE activity at 1 μM. In cells incubated in the presence of 10 nM DM, DOC (10 μM) significantly inhibited ACE production compared with 10 nM DM alone, suggesting that DOC is a partial agonist/partial antagonist in this enzyme system. Protein content of cells or medium was unchanged by steroids at all doses used.

In vivo, adrenalectomized rats showed lower pulmonary ACE compared with intact controls, and when injected with DM (40 μg/d for 4 d) showed a significant (twofold, P < 0.002) increase in lung ACE over oil-injected, adrenalectomized controls; serum ACE did not change. Injection with DOC (40 μg/d) or aldosterone (10 μg/d) had no effect on lung or serum ACE. Over a range (0.6 to 2,000 μg) of concentrations of DM administered daily for 7 d, the dose-response curve of DM for induction of pulmonary ACE mirrored that for thymolysis; for both, half-maximal effects were seen at ∼6 μg DM/d, and plateau levels at 60 μg/d.

We conclude that glucocorticoids are potent inducers of ACE activity in endothelial cells in culture and in rat lung in vivo, and that the action of aldosterone and DOC reflects occupancy of glucocorticoid receptors. This effect may be of (patho)physiological relevance in regulating levels of ACE in local vascular beds, and thereby modulating local levels of the vasoactive peptides angiotensin II and bradykinin.

Full text

PDF
684

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aguilera G., Schirar A., Baukal A., Catt K. J. Circulating angiotensin II and adrenal receptors after nephrectomy. Nature. 1981 Feb 5;289(5797):507–509. doi: 10.1038/289507a0. [DOI] [PubMed] [Google Scholar]
  2. Baxter J. D., Funder J. W. Hormone receptors. N Engl J Med. 1979 Nov 22;301(21):1149–1161. doi: 10.1056/NEJM197911223012104. [DOI] [PubMed] [Google Scholar]
  3. Booyse F. M., Sedlak B. J., Rafelson M. E., Jr Culture of arterial endothelial cells: characterization and growth of bovine aortic cells. Thromb Diath Haemorrh. 1975 Dec 15;34(3):825–839. [PubMed] [Google Scholar]
  4. Caldwell P. R., Seegal B. C., Hsu K. C., Das M., Soffer R. L. Angiotensin-converting enzyme: vascular endothelial localization. Science. 1976 Mar 12;191(4231):1050–1051. doi: 10.1126/science.175444. [DOI] [PubMed] [Google Scholar]
  5. Charney A. N., Silva P., Besarab A., Epstein F. H. Separate effects of aldosterone, DOCA, and methylprednisolone on renal Na-K-ATPase,. Am J Physiol. 1974 Aug;227(2):345–350. doi: 10.1152/ajplegacy.1974.227.2.345. [DOI] [PubMed] [Google Scholar]
  6. Dalakos T. G., Elias A. N., Anderson G. H., Jr, Streeten D. H., Schroeder E. T. Evidence for an angiotensinogenic mechanism of the hypertension of Cushing's syndrome. J Clin Endocrinol Metab. 1978 Jan;46(1):114–118. doi: 10.1210/jcem-46-1-114. [DOI] [PubMed] [Google Scholar]
  7. Davis J. O., Freeman R. H. Mechanisms regulating renin release. Physiol Rev. 1976 Jan;56(1):1–56. doi: 10.1152/physrev.1976.56.1.1. [DOI] [PubMed] [Google Scholar]
  8. Erdös E. G. The angiotensin I converting enzyme. Fed Proc. 1977 Apr;36(5):1760–1765. [PubMed] [Google Scholar]
  9. Friedland J., Setton C., Silverstein E. Angiotensin converting enzyme: induction by steroids in rabbit alveolar macrophages in culture. Science. 1977 Jul 1;197(4298):64–65. doi: 10.1126/science.194311. [DOI] [PubMed] [Google Scholar]
  10. Friedland J., Setton C., Silverstein E. Induction of angiotensin converting enzyme in human monocytes in culture. Biochem Biophys Res Commun. 1978 Aug 14;83(3):843–849. doi: 10.1016/0006-291x(78)91471-7. [DOI] [PubMed] [Google Scholar]
  11. Ganten D., Speck G. The brain renin-angiotensin system: a model for the synthesis of peptides in the brain. Biochem Pharmacol. 1978;27(20):2379–2389. doi: 10.1016/0006-2952(78)90348-9. [DOI] [PubMed] [Google Scholar]
  12. Gimbrone M. A., Jr Culture of vascular endothelium. Prog Hemost Thromb. 1976;3:1–28. [PubMed] [Google Scholar]
  13. Hartree E. F. Determination of protein: a modification of the Lowry method that gives a linear photometric response. Anal Biochem. 1972 Aug;48(2):422–427. doi: 10.1016/0003-2697(72)90094-2. [DOI] [PubMed] [Google Scholar]
  14. Hayes L. W., Goguen C. A., Ching S. F., Slakey L. L. Angiotensin-converting enzyme: accumulation in medium from cultured endothelial cells. Biochem Biophys Res Commun. 1978 Jun 29;82(4):1147–1153. doi: 10.1016/0006-291x(78)90306-6. [DOI] [PubMed] [Google Scholar]
  15. Johnson A. R., Erdos E. G. Angiotensin I converting enzyme (kininase II) in human endothelial cells in culture. Adv Exp Med Biol. 1979;120B:287–295. [PubMed] [Google Scholar]
  16. Krakoff L. R., Selvadurai R., Sutter E. Effect of methylprednisolone upon arterial pressure and the renin angiotensin system in the rat. Am J Physiol. 1975 Feb;228(2):613–617. doi: 10.1152/ajplegacy.1975.228.2.613. [DOI] [PubMed] [Google Scholar]
  17. Maca R. D., Fry G. L., Hoak J. C. The effects of glucocorticoids on cultured human endothelial cells. Br J Haematol. 1978 Apr;38(4):501–509. doi: 10.1111/j.1365-2141.1978.tb01075.x. [DOI] [PubMed] [Google Scholar]
  18. Mendelsohn F. A. Evidence for the local occurrence of angiotensin II in rat kidney and its modulation by dietary sodium intake and converting enzyme blockade. Clin Sci (Lond) 1979 Aug;57(2):173–179. doi: 10.1042/cs0570173. [DOI] [PubMed] [Google Scholar]
  19. Oshima G., Gecse A., Erdös E. G. Angiotensin I-converting enzyme of the kidney cortex. Biochim Biophys Acta. 1974 May 20;350(1):26–37. doi: 10.1016/0005-2744(74)90199-5. [DOI] [PubMed] [Google Scholar]
  20. Piquilloud Y., Reinharz A., Roth M. Studies on the angiotensin converting enzyme with different substrates. Biochim Biophys Acta. 1970 Apr 22;206(1):136–142. doi: 10.1016/0005-2744(70)90090-2. [DOI] [PubMed] [Google Scholar]
  21. Reid I. A., Tu W. H., Otsuka K., Assaykeen T. A., Ganong W. F. Studies concerning the regulation and importance of plasma angiotensinogen concentration in the dog. Endocrinology. 1973 Jul;93(1):107–114. doi: 10.1210/endo-93-1-107. [DOI] [PubMed] [Google Scholar]
  22. Rousseau G. G., Schmit J. P. Structure-activity relationships for glucocorticoids-I. Determination of receptor binding and biological activity. J Steroid Biochem. 1977 Sep;8(9):911–919. doi: 10.1016/0022-4731(77)90187-x. [DOI] [PubMed] [Google Scholar]
  23. Ryan U. S., Clements E., Habliston D., Ryan J. W. Isolation and culture of pulmonary artery endothelial cells. Tissue Cell. 1978;10(3):535–554. doi: 10.1016/s0040-8166(16)30347-0. [DOI] [PubMed] [Google Scholar]
  24. Ryan U. S., Ryan J. W. Angiotensin-converting enzyme: II. Pulmonary endothelial cells in culture. Environ Health Perspect. 1980 Apr;35:171–180. doi: 10.1289/ehp.8035171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Samuels H. H., Tomkins G. M. Relation of steroid structure to enzyme induction in hepatoma tissue culture cells. J Mol Biol. 1970 Aug 28;52(1):57–74. doi: 10.1016/0022-2836(70)90177-4. [DOI] [PubMed] [Google Scholar]
  26. Sennett J. A., Brown R. D., Island D. P., Yarbro L. R., Watson J. T., Slaton P. E., Hollifield J. W., Liddle G. W. Evidence for a new mineralocorticoid in patients with low-renin essential hypertension. Circ Res. 1975 Jun;36(6 Suppl 1):2–9. doi: 10.1161/01.res.36.6.2. [DOI] [PubMed] [Google Scholar]
  27. Swales J. D. Arterial wall or plasma renin in hypertension? Clin Sci (Lond) 1979 Apr;56(4):293–298. doi: 10.1042/cs0560293. [DOI] [PubMed] [Google Scholar]
  28. Ward P. E., Sheridan M. A., Hammon K. J., Erdös E. G. Angiotensin I converting enzyme (kininase II) of the brush border of human and swine intestine. Biochem Pharmacol. 1980 Jun 1;29(11):1525–1529. doi: 10.1016/0006-2952(80)90603-6. [DOI] [PubMed] [Google Scholar]
  29. Yang H. Y., Neff N. H. Distribution and properties of angiotensin converting enzyme of rat brain. J Neurochem. 1972 Oct;19(10):2443–2450. doi: 10.1111/j.1471-4159.1972.tb01298.x. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES