title: Effect of glycyrrhetinic acid on 11 beta-hydroxysteroid dehydrogenase activity in normotensive and hypertensive subjects.
abstract: 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.
authors.affiliation: Department of Medicine, Geert Grooteplein 8, University Medical Center Nijmegen, P. O. Box 9101, 6500 HB Nijmegen, The Netherlands. s.vanuum@endo.azn.nl
authors.forename: Stan H M
authors.initials: SH
authors.lastname: van Uum
authors.forename: Brian R
authors.initials: BR
authors.lastname: Walker
authors.forename: Ad R M M
authors.initials: AR
authors.lastname: Hermus
authors.forename: C G J
authors.initials: CG
authors.lastname: Sweep
authors.forename: Paul
authors.initials: P
authors.lastname: Smits
authors.forename: Peter W
authors.initials: PW
authors.lastname: de Leeuw
authors.forename: Jacques W M
authors.initials: JW
authors.lastname: Lenders
mesh_terms: D042842:11-beta-Hydroxysteroid Dehydrogenases; D000328:Adult; D000704:Analysis of Variance; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001916:Brachial Artery / Q000502:physiology; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D003348:Cortisone / Q000032:analysis; D004311:Double-Blind Method; D005260:Female; D006034:Glycyrrhetinic Acid / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D006973:Hypertension / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012039:Regional Blood Flow; D012463:Saliva / Q000737:chemistry
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D006034:Glycyrrhetinic Acid; D003348:Cortisone; D006854:Hydrocortisone