© 1995 American Heart Association, Inc.
Articles |
Corticosterone Metabolism and Effects on Angiotensin II Receptors in Vascular Smooth Muscle
From the Division of Nephrology, Department of Medicine, Medical University of South Carolina, Charleston.
Abstract It has been postulated that mineralocorticoids can bind to corticosteroid receptors in the kidney, because glucocorticoids are metabolized to inactive compounds. The present study was performed to delineate glucocorticoid metabolism by rat vascular tissue and to determine the activity of these metabolites. Vascular segments converted 25% to 30% of corticosterone (compound B), the major glucocorticoid in the rat, to 11-dehydrocorticosterone (compound A) but not to aldosterone or 6ß-hydroxycorticosterone. In cultured vascular smooth muscle cells, 10% of compound B was converted to compound A, whereas >60% of compound A was converted to compound B. The 11ß-hydroxysteroid dehydrogenase inhibitor carbenoxolone (1 µmol/L) completely blocked conversion in both directions. Whereas 6ß-hydroxycorticosterone did not upregulate angiotensin II receptor binding (a marker for corticosteroid action in vascular smooth muscle), compound A caused concentration-dependent upregulation. Compound A was almost (75%) as effective and as potent as compound B in upregulating angiotensin II binding. Upregulation elicited by exposure to compound A persisted in the presence of 1 µmol/L carbenoxolone, which completely prevented the conversion of compound A to compound B. Compound A, even in the presence of carbenoxolone, effected other glucocorticoid actions by inhibiting cell growth and potentiating angiotensin II–stimulated inositol phosphate formation. In summary, compound B and compound A are interconverted in vascular tissue, and the latter displays significant glucocorticoid action. The concentration excess of compound B in the circulation and the activity of its metabolite compound A will make it difficult for mineralocorticoids to gain access to corticosteroid receptors in the vasculature.
Key Words: angiotensin II • vascular smooth muscle • corticosterone • 11-dehydrocorticosterone
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