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

Abstract

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. © 2008 American Journal of Hypertension, Ltd.