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.
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 hypertensivepatients 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.
Authors: Matthew A Bailey; Eilidh Craigie; Dawn E W Livingstone; Yuri V Kotelevtsev; Emad A S Al-Dujaili; Christopher J Kenyon; John J Mullins Journal: Hypertension Date: 2011-01-31 Impact factor: 10.190
Authors: Fiona Broughton Pipkin; Hiten D Mistry; Chandrima Roy; Bernhard Dick; Jason Waugh; Rebecca Chikhi; Lesia O Kurlak; Markus G Mohaupt Journal: Endocr Connect Date: 2015-09-16 Impact factor: 3.335
Authors: Christiane Drechsler; Eberhard Ritz; Andreas Tomaschitz; Stefan Pilz; Stephan Schönfeld; Katja Blouin; Martin Bidlingmaier; Fabian Hammer; Vera Krane; Winfried März; Bruno Allolio; Martin Fassnacht; Christoph Wanner Journal: Eur Heart J Date: 2012-12-04 Impact factor: 29.983
Authors: Michael S Sagmeister; Angela E Taylor; Anthony Fenton; Nadezhda A Wall; Dimitrios Chanouzas; Peter G Nightingale; Charles J Ferro; Wiebke Arlt; Paul Cockwell; Rowan S Hardy; Lorraine Harper Journal: Clin Endocrinol (Oxf) Date: 2018-11-15 Impact factor: 3.478