In Vivo 11β-HSD-2 Activity: Variability, Salt-Sensitivity, and Effect of Licorice

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 38; no. 6; pp. 1330 - 1336
• Main Authors: Ferrari, Paolo, Sansonnens, Aurelie, Dick, Bernhard, Frey, Felix J.
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.12.2001; Hagerstown, MD Lippincott
• Subjects: Biological and medical sciences; Blood vessels and receptors; Fundamental and applied biological sciences. Psychology; Vertebrates: cardiovascular system; Human; Urine; Enzyme; Isozyme; Variability; Exploration; Cortisol; Enoxolone; Glucocorticoid; Salt; Sensitivity; Enzymatic activity; Diet; Sodium; 11β-Hydroxysteroid dehydrogenase; Blood pressure; Circulatory system; Oxidoreductases; Technique; Comparative study
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/hy1101.096112

Loss-of-function mutations or inhibition of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD-2) results in overstimulation of the mineralocorticoid receptor by cortisol and causes salt-sensitive hypertension. Traditionally, 11β-HSD-2 activity has been assessed by measurement of the urinary cortisol metabolite ratio (tetrahydrocortisol [THF]+5α-THF)/tetrahydrocortisone (THE). Recently, the ratio of urinary free glucocorticoids, UFF/UFE, has been suggested to be a more reliable parameter, an aspect that has not been investigated systematically. Steroid metabolites were measured repeatedly by gas chromatography–mass spectrometry in 20 healthy subjects at baseline and after 1 week each of a 30- or 180-mmol/d of sodium diet or 500 mg/d of glycyrrhetinic acid. Intraindividual coefficients of variation from 3 random urine collections for (THF+5α-THF)/THE and UFF/UFE ratios were 11±9% and 25±14% (P <0.001). (THF+5α-THF)/THE was more sensitive than UFF/UFE for detection of glycyrrhetinic acid–induced increases higher than the upper 95% confidence interval of the coefficient of variation of the corresponding ratio. Low- or high-salt diet did not alter either ratio. Mean (THF+5α-THF)/THE but not UFF/UFE was higher in salt-sensitive than salt-resistant subjects. Absolute glycyrrhetinic acid–related increase in (THF+5α-THF)/THE but not UFF/UFE was higher in salt-sensitive than salt-resistant subjects and correlated with changes in mean BP. Intraindividual variability of (THF+5α-THF)/THE is lower than that of UFF/UFE. The UFF/UFE ratio does not appear to be more sensitive than (THF+5α-THF)/THE for detection of decreased 11β-HSD-2 activity. The (THF+5α-THF)/THE ratio better discriminates between salt-sensitive and salt-resistant subjects. Together with BP responses to glycyrrhetinic acid, these findings support a pivotal role of 11β-HSD-2 in salt sensitivity.