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


CONCLUSIONS
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.
Henschkowski
Jana
J
Department of Geriatrics, Inselspital University Hospital, Berne, Switzerland.
Stuck
Andreas E
AE
Frey
Brigitte M
BM
Gillmann
Gerhard
G
Dick
Bernhard
B
Frey
Felix J
FJ
Mohaupt
Markus G
MG
D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000652:urine*; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006973:Hypertension / Q000097:blood / Q000201:enzymology*; D008297:Male; D008875:Middle Aged
D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D006854:Hydrocortisone