Glycyrrhetinic acid decreases plasma potassium concentrations in patients with anuria.
ABSTRACT. Licorice-associated hypertension is thought to be due to increased renal sodium retention. The active compound of licorice, glycyrrhetinic acid (GA), inhibits renal 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) and by that mechanism increases access of cortisol to the mineralocorticoid receptor that causes renal sodium retention and potassium loss. In addition, a direct vascular effect of 11beta-HSD activity has recently been incriminated to promote hypertension, a contention based on in vitro observations. This investigation was designed to establish whether this extrarenal effect of 11beta-HSD is relevant for BP regulation and potassium concentrations in plasma. In a prospective, double-blind, cross-over study, seven patients with anuria on chronic hemodialysis were randomly assigned after a baseline period of 2 wk to placebo or GA (1 g/d) for 2 wk, separated by a washout phase of 3 wk. The ratio of plasma cortisol/cortisone, determined by gas chromatography-mass spectrometry, increased in all patients after GA intake (F = 9.705; P < 0.004), which indicates inhibition of 11beta-HSD. Twenty-four-hour BP values did not change throughout the study. The increase of the plasma cortisol/cortisone ratio was paralleled by a decline in the plasma potassium concentration in every patient. The mean +/- SD plasma potassium concentration decreased from 5.5 +/- 0.6 mM/L at baseline to 4.9 +/- 0.7 and 4.5 +/- 0.8 mM/L after 1 and 2 wk on GA, respectively (F = 9.934, P < 0.003). Extrarenal 11beta-HSD activity influences serum potassium concentrations but does not regulate BP independently of renal sodium retention.
Serra
Andreas
A
University Hospital of Berne, Berne, Switzerland.
Uehlinger
Dominik E
DE
University Hospital of Berne, Berne, Switzerland.
Ferrari
Paolo
P
University Hospital of Berne, Berne, Switzerland.
Dick
Bernhard
B
University Hospital of Berne, Berne, Switzerland.
Frey
Brigitte M
BM
University Hospital of Berne, Berne, Switzerland.
Frey
Felix J
FJ
University Hospital of Berne, Berne, Switzerland.
Vogt
Bruno
B
University Hospital of Berne, Berne, Switzerland.
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000368:Aged; D001002:Anuria / Q000097:blood* / Q000188:drug therapy* / Q000628:therapy; D001794:Blood Pressure / Q000187:drug effects; D003348:Cortisone / Q000097:blood; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006034:Glycyrrhetinic Acid / Q000627:therapeutic use*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006913:Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors*; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D011188:Potassium / Q000097:blood*; D011446:Prospective Studies; D006435:Renal Dialysis; D013997:Time Factors
D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D006034:Glycyrrhetinic Acid; D011188:Potassium; D003348:Cortisone; D006854:Hydrocortisone