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(Hypertension. 1999;34:1123-1128.)
© 1999 American Heart Association, Inc.

Scientific Contributions

11ß-Hydroxysteroid Dehydrogenase and Corticosteroid Action in Lyon Hypertensive Rats

Susan A. Lloyd-MacGilp; Susan M. Nelson; Marine Florin; Ming Lo; Joanna McKinnell; Jean Sassard; Christopher J. Kenyon

From the Molecular Medicine Centre, University of Edinburgh, UK (S.A.L-M., S.M.N., J.M., C.J.K.), and Faculty of Pharmacy, Centre National de la Recherche Scientifique ESA 5014, Lyon, France (M.F., M.L., J.S.).

Correspondence to Dr C.J. Kenyon, Molecular Medicine Centre, Western General Hospital, Edinburgh, EH4 2XU, UK. E-mail cjk{at}srv0.med.ed.ac.uk

Abstract—Adrenocorticosteroid activity in Lyon hypertensive (LH) and low blood pressure (LL) rat strains differ in several respects. Abnormal activity of 11ß-hydroxysteroid dehydrogenase enzymes (11ß-HSD1 and 11ß-HSD2), which interconvert corticosterone and inactive 11-dehydrocorticosterone, might contribute to the LH phenotype by regulating corticosteroid hormone access to receptors. 11ß-HSD2 (expressed in kidney but not liver) prevents endogenous glucocorticoids from binding to mineralocorticoid receptors. 11ß-HSD1 (expressed in liver and kidney) favors active glucocorticoid formation from 11-dehydrocorticosterone. 11ß-HSD properties in LH and LL have been compared by several approaches: (1) 11ßHSD activities have been measured in vitro as corticosterone dehydrogenation and in vivo as interconversion of injected cortisol and cortisone; (2) the effects of cortisol and cortisone on urine electrolytes and volume have been measured; and (3) 11ß-HSD mRNA expression has been measured by in situ hybridization. 11ß-HSD2 enzyme activities in LH and LL rats were similar and urinary cortisone:cortisol ratios were not different after cortisol injection. Cortisol caused a natriuresis and kaliuresis in both strains, with a slightly reduced response in LH rats. Renal 11ß-HSD2 mRNA expression was slightly lower in LH rats. 11ß-HSD1 was less active in LH than LL rats: enzyme activities were lower in tissue extracts; urinary cortisone:cortisol was lower in LL rats after cortisone injections; cortisone increased urine volume in LL but not LH rats; and mRNA levels tended to be lower in LH tissues. We conclude that 11ß-HSD1 is impaired in LH rats. The LH phenotype of heavier adrenals, raised corticosterone, and reduced thymus weight is similar to that described for 11ß-HSD1 knockout mice.

Key Words: glucocorticoids • mineralocorticoids • corticosterone • cortisol • cortisone • renal function

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