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

Henschkowski, Jana; Stuck, Andreas E; Frey, Brigitte M; Gillmann, Gerhard; Dick, Bernhard; Frey, Felix J; Mohaupt, Markus G (2008). Age-dependent decrease in 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) activity in hypertensive patients. American journal of hypertension, 21(6), pp. 644-9. Oxford: Oxford University Press 10.1038/ajh.2008.152

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BACKGROUND: 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of General Internal Medicine (DAIM) > Geriatric Clinic
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Nephrology and Hypertension
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Social and Preventive Medicine

UniBE Contributor:

Stuck, Andreas; Frey, Brigitte; Gillmann, Gerhard; Frey, Felix Julius and Mohaupt, Markus

ISSN:

0895-7061

ISBN:

18443572

Publisher:

Oxford University Press

Language:

English

Submitter:

Markus Georg Mohaupt

Date Deposited:

04 Oct 2013 15:04

Last Modified:

27 Apr 2018 10:39

Publisher DOI:

10.1038/ajh.2008.152

PubMed ID:

18443572

Web of Science ID:

000255841800012

BORIS DOI:

10.7892/boris.27794

URI:

https://boris.unibe.ch/id/eprint/27794 (FactScience: 111528)

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