PMID- 11834140
OWN - NLM
STAT- MEDLINE
DCOM- 20020408
LR  - 20220317
IS  - 0143-5221 (Print)
IS  - 0143-5221 (Linking)
VI  - 102
IP  - 2
DP  - 2002 Feb
TI  - Effect of glycyrrhetinic acid on 11 beta-hydroxysteroid dehydrogenase activity in 
      normotensive and hypertensive subjects.
PG  - 203-11
AB  - The 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) isoenzymes catalyse the 
      interconversion of cortisol and cortisone. Type 1 11 beta-HSD mainly converts 
      cortisone into active cortisol. Type 2 11 beta-HSD inactivates cortisol in 
      mineralocorticoid target tissues, and its activity can be inhibited by 
      glycyrrhetinic acid (GA). Inactivation of cortisol to cortisone is impaired in a 
      subgroup of patients with primary hypertension. To study where this defect is 
      located, we measured cortisol and cortisone concentrations in arterial plasma, in 
      saliva and across the forearm at baseline and after administration of GA in 
      normotensive and hypertensive subjects. GA (500 mg) or placebo was administered 
      orally to 20 normotensive subjects in a placebo-controlled double-blind fashion. 
      Further, we compared the effect of GA in 20 patients with primary hypertension 
      with that in 20 normotensive subjects. Cortisol and cortisone were measured in 
      plasma from the brachial artery and vein and in saliva. Samples were obtained at 
      0, 90 and 150 min. Forearm blood flow (FBF) was measured simultaneously. Forearm 
      production of corticosteroid hormones was assessed by multiplying the 
      arteriovenous difference in corticosteroid concentration by FBF. The 
      cortisol/cortisone ratio in arterial plasma remained at baseline levels after 
      placebo (4.9 +/- 1.2; mean +/- S.D.), while after GA the ratio increased 
      similarly in normotensive subjects (12.3 +/- 3.4) and in hypertensive patients 
      (12.2 +/- 3.7). A similar effect of GA on the salivary cortisol/cortisone ratio 
      was found. In both normotensive subjects and hypertensive patients no forearm 
      production of cortisol or cortisone could be demonstrated, either at baseline or 
      after administration of GA. Thus, both before and after GA administration, we did 
      not find any difference in systemic and salivary 11 beta-HSD type 2 activity 
      between subjects with primary hypertension and normotensive controls. Further, 
      both at baseline and after GA administration we were not able to demonstrate net 
      inactivation or re-activation of cortisol and cortisone by the 11 beta-HSD 
      isoenzymes in the forearm in either normotensive or primary hypertensive 
      subjects.
FAU - van Uum, Stan H M
AU  - van Uum SH
AD  - Department of Medicine, Geert Grooteplein 8, University Medical Center Nijmegen, 
      P. O. Box 9101, 6500 HB Nijmegen, The Netherlands. s.vanuum@endo.azn.nl
FAU - Walker, Brian R
AU  - Walker BR
FAU - Hermus, Ad R M M
AU  - Hermus AR
FAU - Sweep, C G J
AU  - Sweep CG
FAU - Smits, Paul
AU  - Smits P
FAU - de Leeuw, Peter W
AU  - de Leeuw PW
FAU - Lenders, Jacques W M
AU  - Lenders JW
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Clin Sci (Lond)
JT  - Clinical science (London, England : 1979)
JID - 7905731
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - EC 1.1.- (Hydroxysteroid Dehydrogenases)
RN  - EC 1.1.1.146 (11-beta-Hydroxysteroid Dehydrogenases)
RN  - P540XA09DR (Glycyrrhetinic Acid)
RN  - V27W9254FZ (Cortisone)
RN  - WI4X0X7BPJ (Hydrocortisone)
SB  - IM
MH  - 11-beta-Hydroxysteroid Dehydrogenases
MH  - Adult
MH  - Analysis of Variance
MH  - Anti-Inflammatory Agents, Non-Steroidal/*pharmacology
MH  - Brachial Artery/physiology
MH  - Case-Control Studies
MH  - Chromatography, High Pressure Liquid
MH  - Cortisone/analysis
MH  - Double-Blind Method
MH  - Female
MH  - Glycyrrhetinic Acid/*pharmacology
MH  - Humans
MH  - Hydrocortisone/analysis
MH  - Hydroxysteroid Dehydrogenases/*metabolism
MH  - Hypertension/*metabolism
MH  - Male
MH  - Middle Aged
MH  - Regional Blood Flow
MH  - Saliva/chemistry
EDAT- 2002/02/09 10:00
MHDA- 2002/04/09 10:01
CRDT- 2002/02/09 10:00
PHST- 2002/02/09 10:00 [pubmed]
PHST- 2002/04/09 10:01 [medline]
PHST- 2002/02/09 10:00 [entrez]
AID - 10.1042/cs20010194 [doi]
PST - ppublish
SO  - Clin Sci (Lond). 2002 Feb;102(2):203-11. doi: 10.1042/cs20010194.