© 1998 by European Society of Cardiology
Copyright © 1998, European Society of Cardiology
The role of 11β-hydroxysteroid dehydrogenase in the pathogenesis of hypertension
aDivision of General Internal Medicine, Department of Medicine, St. Radboud University Hospital, University of Nijmegen, PO Box 9101, 6500 HB Nijmegen, Netherlands
bDivision of Endocrinology, Department of Medicine, University of Nijmegen, Nijmegen, Netherlands
cDepartment of Pharmacology, University of Nijmegen, Nijmegen, Netherlands
* Corresponding author. Tel.: +31 (24) 3614763; fax: +31 (24) 3541734; e-mail: s.vanuum@aig.azn.nl
The two 11β-hydroxysteroid dehydrogenase (11β-HSD) isozymes catalyze the interconversion of cortisol and cortisone. Type 1 11β-HSD (11β-HSD1) has bidirectional activity, while type 2 11β-HSD (11β-HSD2) mainly converts cortisol into cortisone. Of these two hormones only cortisol has affinity to mineralocorticoid receptors (MRs) and thus induces mineralocorticoid effects. A normal activity of 11β-HSD2 is crucial for prevention of mineralocorticoid activity of cortisol. Absent or decreased 11β-HSD2 activity results in cortisol-mediated hypermineralocorticoid hypertension. In several hypertensive syndromes a decreased 11β-HSD2 activity has been described as the pathogenetic mechanism of the increased blood pressure. In the apparent mineralocorticoid excess (AME) syndrome type 1, absence of 11β-HSD2 activity is caused by mutations in the gene coding for 11β-HSD2. In licorice-induced hypertension glycyrrhetinic acid, the active substituent of licorice, inhibits 11β-HSD2 resulting in an acquired hypermineralocorticoid state. 11β-HSD2 activity is not decreased in glucocorticoid hypertension (Cushing's syndrome). In essential hypertension some evidence for decreased systemic and skin activity of 11β-HSD1 and/or 11β-HSD2 has been found, while renal activity of both isozymes appears to be normal. 11β-HSD2 activity is also present in cardiovascular myocytes of humans and dogs, and inhibition of 11β-HSD potentiates the vascular response to catecholamines. Although MRs in the central nervous system have been incriminated in the pathogenesis of mineralocorticoid hypertension, a pathophysiological role for 11β-HSD2 has not yet been described. Finally, in the placenta 11β-HSD2 reduces fetal exposure to maternal glucocorticoids and a decreased activity of this isozyme may result in low birth weight and increased risk of high blood pressure at adult age.
KEYWORDS 11β-Hydroxysteroid dehydrogenase; Hypertension; Glycyrrhetinic acid; Licorice; AME-syndrome; Cortisol; Aldosterone
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