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Age-dependent decrease in 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) activity in hypertensive patients.

AbstractBACKGROUND:
The prevalence of arterial hypertension lacking a defined underlying cause increases with age. Age-related arterial hypertension is insufficiently understood, yet known characteristics suggest an aldosterone-independent activation of the mineralocorticoid receptor. Therefore, we hypothesized that 11beta-HSD2 activity is age-dependently impaired, resulting in a compromised intracellular inactivation of cortisol (F) with F-mediated mineralocorticoid hypertension.
METHODS:
Steroid hormone metabolites in 24-h urine samples of 165 consecutive hypertensive patients were analyzed for F and cortisone (E), and their TH-metabolites tetrahydro-F (THF), 5alphaTHF, TH-deoxycortisol (THS), and THE by gas chromatography-mass spectroscopy. Apparent 11beta-HSD2 and 11beta-hydroxylase activity and excretion of F metabolites were assessed.
RESULTS:
In 72 female and 93 male patients aged 18-84 years, age correlated positively with the ratios of (THF + 5alphaTHF)/THE (P = 0.065) and F/E (P < 0.002) suggesting an age-dependent reduction in the apparent 11beta-HSD2 activity, which persisted (F/E; P = 0.020) after excluding impaired renal function. Excretion of F metabolites remained age-independent most likely as a consequence of an age-dependent diminished apparent 11beta-hydroxylase activity (P = 0.038).
CONCLUSION:
Reduced 11beta-HSD2 activity emerges as a previously unrecognized risk factor contributing to the rising prevalence of arterial hypertension in elderly. This opens new perspectives for targeted treatment of age-related hypertension.
AuthorsJana Henschkowski, Andreas E Stuck, Brigitte M Frey, Gerhard Gillmann, Bernhard Dick, Felix J Frey, Markus G Mohaupt
JournalAmerican journal of hypertension (Am J Hypertens) Vol. 21 Issue 6 Pg. 644-9 (Jun 2008) ISSN: 0895-7061 [Print] United States
PMID18443572 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • 11-beta-Hydroxysteroid Dehydrogenase Type 2
  • Hydrocortisone
Topics
  • 11-beta-Hydroxysteroid Dehydrogenase Type 2 (urine)
  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Female
  • Humans
  • Hydrocortisone (blood)
  • Hypertension (blood, enzymology)
  • Male
  • Middle Aged

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