This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ferrari, P. Articles by Frey, F. J. Search for Related Content PubMed PubMed Citation Articles by Ferrari, P. Articles by Frey, F. J. Related Collections Hypertension - basic studies Clinical Studies Other diagnostic testing

(Hypertension. 2001;38:1330.)
© 2001 American Heart Association, Inc.

Scientific Contributions

In Vivo 11ß-HSD-2 Activity

Variability, Salt-Sensitivity, and Effect of Licorice

Paolo Ferrari; Aurelie Sansonnens; Bernhard Dick; Felix J. Frey

From the Division of Nephrology and Hypertension, Inselspital, University of Berne, Switzerland.

Correspondence to Paolo Ferrari, MD, Division of Nephrology and Hypertension, Inselspital, University of Berne, Freiburgstr 10, 3010 Berne, Switzerland. E-mail paolo.ferrari{at}insel.ch

Loss-of-function mutations or inhibition of 11ß-hydroxysteroid dehydrogenase type 2 (11ß-HSD-2) results in overstimulation of the mineralocorticoid receptor by cortisol and causes salt-sensitive hypertension. Traditionally, 11ß-HSD-2 activity has been assessed by measurement of the urinary cortisol metabolite ratio (tetrahydrocortisol [THF]+5-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+5-THF)/THE and UFF/UFE ratios were 11±9% and 25±14% (P<0.001). (THF+5-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+5-THF)/THE but not UFF/UFE was higher in salt-sensitive than salt-resistant subjects. Absolute glycyrrhetinic acid–related increase in (THF+5-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+5-THF)/THE is lower than that of UFF/UFE. The UFF/UFE ratio does not appear to be more sensitive than (THF+5-THF)/THE for detection of decreased 11ß-HSD-2 activity. The (THF+5-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 11ß-HSD-2 in salt sensitivity.

Key Words: hypertension, salt-sensitive • sodium, dietary • 11ß-hydroxysteroid dehydrogenase • urine • glycyrrhetinic acid

This article has been cited by other articles:

				R. Alikhani-Koupaei, F. Fouladkou, P. Fustier, B. Cenni, A. M. Sharma, H.-C. Deter, B. M. Frey, and F. J. Frey Identification of polymorphisms in the human 11beta-hydroxysteroid dehydrogenase type 2 gene promoter: functional characterization and relevance for salt sensitivity FASEB J, November 1, 2007; 21(13): 3618 - 3628. [Abstract] [Full Text] [PDF]

				A. G. Atanasov, I. D. Ignatova, L. G. Nashev, B. Dick, P. Ferrari, F. J. Frey, and A. Odermatt Impaired Protein Stability of 11beta-Hydroxysteroid Dehydrogenase Type 2: A Novel Mechanism of Apparent Mineralocorticoid Excess J. Am. Soc. Nephrol., April 1, 2007; 18(4): 1262 - 1270. [Abstract] [Full Text] [PDF]

				G. Morineau, V. Sulmont, R. Salomon, B. Fiquet-Kempf, X. Jeunemaitre, J. Nicod, and P. Ferrari Apparent Mineralocorticoid Excess: Report of Six New Cases and Extensive Personal Experience J. Am. Soc. Nephrol., November 1, 2006; 17(11): 3176 - 3184. [Abstract] [Full Text] [PDF]

				K. Strojek, J. Nicod, P. Ferrari, W. Grzeszczak, J. Gorska, B. Dick, F. Frey, and E. Ritz Salt-sensitive blood pressure--an intermediate phenotype predisposing to diabetic nephropathy? Nephrol. Dial. Transplant., October 1, 2005; 20(10): 2113 - 2119. [Abstract] [Full Text] [PDF]

				N. Draper and P. M Stewart 11{beta}-Hydroxysteroid dehydrogenase and the pre-receptor regulation of corticosteroid hormone action J. Endocrinol., August 1, 2005; 186(2): 251 - 271. [Abstract] [Full Text] [PDF]

				P. Meneton, X. Jeunemaitre, H. E. de Wardener, and G. A. Macgregor Links Between Dietary Salt Intake, Renal Salt Handling, Blood Pressure, and Cardiovascular Diseases Physiol Rev, April 1, 2005; 85(2): 679 - 715. [Abstract] [Full Text] [PDF]

				N. Glorioso, F. Filigheddu, P. P. Parpaglia, A. Soro, C. Troffa, G. Argiolas, and P. Mulatero 11{beta}-Hydroxysteroid dehydrogenase type 2 activity is associated with left ventricular mass in essential hypertension Eur. Heart J., March 1, 2005; 26(5): 498 - 504. [Abstract] [Full Text] [PDF]

				S. Ganapathipillai, G. Laval, I. S. Hoffmann, A. M. Castejon, J. Nicod, B. Dick, F. J. Frey, B. M. Frey, L. X. Cubeddu, and P. Ferrari CYP11B2-CYP11B1 Haplotypes Associated with Decreased 11{beta}-Hydroxylase Activity J. Clin. Endocrinol. Metab., February 1, 2005; 90(2): 1220 - 1225. [Abstract] [Full Text] [PDF]

				B. Bocchi, S. Kenouch, M. Lamarre-Cliche, M. Muffat-Joly, M. H. Capron, J. Fiet, G. Morineau, M. Azizi, J. P. Bonvalet, and N. Farman Impaired 11-{beta} Hydroxysteroid Dehydrogenase Type 2 Activity in Sweat Gland Ducts in Human Essential Hypertension Hypertension, April 1, 2004; 43(4): 803 - 808. [Abstract] [Full Text] [PDF]

				M. N. Kerstens, F. G. H. van der Kleij, A. H. Boonstra, W. J. Sluiter, J. Koerts, G. Navis, and R. P. F. Dullaart Salt Loading Affects Cortisol Metabolism in Normotensive Subjects: Relationships with Salt Sensitivity J. Clin. Endocrinol. Metab., September 1, 2003; 88(9): 4180 - 4185. [Abstract] [Full Text] [PDF]

				R. Norregaard, T. R. Uhrenholt, C. Bistrup, O. Skott, and B. L. Jensen Stimulation of 11-{beta}-hydroxysteroid dehydrogenase type 2 in rat colon but not in kidney by low dietary NaCl intake Am J Physiol Renal Physiol, August 1, 2003; 285(2): F348 - F358. [Abstract] [Full Text] [PDF]

				E. Elinav and T. Chajek-Shaul Licorice Consumption Causing Severe Hypokalemic Paralysis Mayo Clin. Proc., June 1, 2003; 78(6): 767 - 768. [Abstract] [PDF]

				B. Vogt, B. M. Frey, and F. J. Frey Reply Nephrol. Dial. Transplant., March 1, 2003; 18(3): 620 - 621. [Full Text] [PDF]

				P. Ferrari, M. G. Bianchetti, A. Sansonnens, and F. J. Frey Modulation of Renal Calcium Handling by 11{beta}-Hydroxysteroid Dehydrogenase Type 2 J. Am. Soc. Nephrol., October 1, 2002; 13(10): 2540 - 2546. [Abstract] [Full Text] [PDF]

				A. T. Stauffer, M. K. Rochat, B. Dick, F. J. Frey, and A. Odermatt Chenodeoxycholic Acid and Deoxycholic Acid Inhibit 11beta -Hydroxysteroid Dehydrogenase Type 2 and Cause Cortisol-induced Transcriptional Activation of the Mineralocorticoid Receptor J. Biol. Chem., July 12, 2002; 277(29): 26286 - 26292. [Abstract] [Full Text] [PDF]

				B. Vogt, B. Dick, H.-P. Marti, F. J. Frey, and B. M. Frey Reduced 11{beta}-hydroxysteroid dehydrogenase activity in experimental nephrotic syndrome Nephrol. Dial. Transplant., May 1, 2002; 17(5): 753 - 758. [Abstract] [Full Text] [PDF]