Angiotensin administration stimulates renal 11 beta-hydroxysteroid dehydrogenase activity in healthy men.
BACKGROUND
We examined whether acute administration of angiotensin modulates the activity of 11 beta-hydroxysteroid dehydrogenase (11 beta HSD), the intracellular enzyme catalyzing the interconversion between the hormonally active cortisol and inactive cortisone.


METHODS
Twenty-one male healthy subjects were examined after 1 week of a low- and high-salt diet (50 and 200 mmol/day, respectively). Separate infusions of angiotensin I (Ang I) and II (Ang II) were administered, both at rates of 4 and 8 ng/kg/min. The ratios of tetrahydrocortisol + allotetrahydrocortisol/tetrahydrocortisone (THF + allo-THF/THE) and of free cortisol/free cortisone (UFF/UFE) in urine were measured as indices of overall 11 beta HSD set point and activity of renal 11 beta HSD type 2, respectively. Glomerular filtration rate (GFR) was measured by constant infusion of (125)I-iothalamate.


RESULTS
Ang I and Ang II infusion dose-dependently increased mean arterial blood pressure (MAP) and plasma aldosterone, and decreased plasma renin activity (PRA) and GFR at both diets. Ang I and Ang II infusion resulted in a dose-dependent decrease in the excretion of UFF, UFE, and of the UFF/UFE ratio at both diets, without changing the urinary (THF + allo-THF)/THE ratio. Salt restriction did not affect these 11 beta HSD variables, but was accompanied by a decrease in UFF and UFE excretion.


CONCLUSIONS
This study suggests that acute angiotensin administration stimulates the activity of 11 beta HSD type 2 in human kidney. Angiotensin might therefore exert a dual effect on the mineralocorticoid receptor (i.e., an indirect agonistic effect by increasing aldosterone availability and a direct or indirect antagonistic effect by stimulation of renal 11 beta HSD type 2 activity).
Kerstens
Michiel N
MN
Department of Endocrinology, University Hospital Groningen, Groningen, The Netherlands. m.n.kerstens@int.azg.nl
van der Kleij
Frank G H
FG
Boonstra
Arnold H
AH
Sluiter
Wim J
WJ
van der Molen
Jan C
JC
Navis
Gerjan
G
Dullaart
Robin P F
RP
D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000378:metabolism*; D000328:Adult; D000803:Angiotensin I / Q000008:administration & dosage*; D000804:Angiotensin II / Q000008:administration & dosage*; D003348:Cortisone / Q000378:metabolism / Q000652:urine; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism / Q000652:urine; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology*; D008297:Male
D000804:Angiotensin II; D000803:Angiotensin I; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D003348:Cortisone; D006854:Hydrocortisone