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Age-dependent Decrease in 11β-Hydroxysteroid Dehydrogenase Type 2 (11β-HSD2) Activity in Hypertensive Patients

Henschkowski, Jana ; Stuck, Andreas E. ; Frey, Brigitte M. ; Gillmann, Gerhard ; Dick, Bernhard ; Frey, Felix J. ; Mohaupt, Markus G.

In: American Journal of Hypertension, 2008, vol. 21, no. 6, p. 644-649

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    Titre
    • Age-dependent Decrease in 11β-Hydroxysteroid Dehydrogenase Type 2 (11β-HSD2) Activity in Hypertensive Patients
    Auteur
    • Henschkowski, Jana. Department of Geriatrics, Inselspital University Hospital, Berne, Switzerland
    • Stuck, Andreas E.. Department of Geriatrics, Inselspital University Hospital, Berne, Switzerland
    • Frey, Brigitte M.. Department of Nephrology and Hypertension, University Hospital of Bern, Berne, Switzerland
    • Gillmann, Gerhard. Institute of Social and Preventive Medicine, University of Bern, Berne, Switzerland
    • Dick, Bernhard. Department of Nephrology and Hypertension, University Hospital of Bern, Berne, Switzerland
    • Frey, Felix J.. Department of Nephrology and Hypertension, University Hospital of Bern, Berne, Switzerland
    • Mohaupt, Markus G.. Department of Nephrology and Hypertension, University Hospital of Bern, Berne, Switzerland
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • American Journal of Hypertension, 2008, vol. 21, no. 6, p. 644-649. Oxford University Press
    Autre version électronique
    Classification
    • Santé
    Identifiant OAI-PMH
    • oai:doc.rero.ch:304949
    Summary
    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 11β-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), 5αTHF, TH-deoxycortisol (THS), and THE by gas chromatography-mass spectroscopy. Apparent 11β-HSD2 and 11β-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 + 5αTHF)/THE (P = 0.065) and F/E (P < 0.002) suggesting an age-dependent reduction in the apparent 11β-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 11β-hydroxylase activity (P = 0.038). Conclusion Reduced 11β-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