The role of 11 beta-hydroxysteroid dehydrogenase in the pathogenesis of hypertension

Cardiovasc Res. 1998 Apr;38(1):16-24. doi: 10.1016/s0008-6363(97)00299-x.

Abstract

The two 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) isozymes catalyze the interconversion of cortisol and cortisone. Type 1 11 beta-HSD (11 beta-HSD1) has bidirectional activity, while type 2 11 beta-HSD (11 beta-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 11 beta-HSD2 is crucial for prevention of mineralocorticoid activity of cortisol. Absent or decreased 11 beta-HSD2 activity results in cortisol-mediated hypermineralocorticoid hypertension. In several hypertensive syndromes a decreased 11 beta-HSD2 activity has been described as the pathogenetic mechanism of the increased blood pressure. In the apparent mineral corticoid excess (AME) syndrome type 1, absence of 11 beta-HSD2 activity is caused by mutations in the gene coding for 11 beta-HSD2. In licorice-induced hypertension glycyrrhetinic acid, the active substituent of licorice, inhibits 11 beta-HSD2 resulting in an acquired hypermineralocorticoid state. 11 beta-HSD2 activity is not decreased in glucocorticoid hypertension (Cushing's syndrome). In essential hypertension some evidence for decreased systemic and skin activity of 11 beta-HSD1 and/or 11 beta-HSD2 has been found, while renal activity of both isozymes appears to be normal. 11 beta-HSD2 activity is also present in cardiovascular myocytes of humans and dogs, and inhibition of 11 beta-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 11 beta-HSD2 has not yet been described. Finally, in the placenta 11 beta-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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • 11-beta-Hydroxysteroid Dehydrogenases
  • Cortisone / metabolism
  • Glycyrrhetinic Acid / metabolism
  • Humans
  • Hydrocortisone / metabolism
  • Hydroxysteroid Dehydrogenases / physiology*
  • Hypertension / enzymology*
  • Isoenzymes / physiology
  • Receptors, Mineralocorticoid / metabolism

Substances

  • Isoenzymes
  • Receptors, Mineralocorticoid
  • Hydroxysteroid Dehydrogenases
  • 11-beta-Hydroxysteroid Dehydrogenases
  • Glycyrrhetinic Acid
  • Cortisone
  • Hydrocortisone