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Furosemide and 11beta-hydroxysteroid dehydrogenase activity, in man.

Title: Furosemide and 11beta-hydroxysteroid dehydrogenase activity, in man.
Authors: PALERMO M; SHACKLETON CH; SORBA G; COSSU M; ROITMAN E; DELITALA G.; ARMANINI, DECIO; SCARONI, CARLA
Contributors: Palermo, M; Armanini, Decio; Shackleton, Ch; Sorba, G; Cossu, M; Roitman, E; Scaroni, Carla; Delitala, G.
Publisher Information: JOHANN AMBROSIUS BARTH VERLAG MEDIZINVERLAGE HEIDELBERG GMBH, RUEDIGERSTR 14, D-70469 STUTTGART, GERMANY
Publication Year: 2002
Collection: Padua Research Archive (IRIS - Università degli Studi di Padova)
Description: Mineralocorticoid receptors possess the same affinity for aldosterone and for cortisol and preferential binding of aldosterone is modulated by the 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) enzyme, which converts cortisol to its inactive metabolite cortisone. Several endogenous or exogenous compounds able to inhibit the enzyme have been described and, as a consequence, produce the syndrome of apparent mineralocorticoid excess (AME) characterized by hypertension, hypokalemia, volume repletion and suppression of the renin-angiotensin-aldosterone system. High doses of furosemide, a diuretic that works in the luminal surface of the thick ascending limb of Henle's loop, have been reported to inhibit 11 beta-OHSD activity to the same extent as licorice in vivo and in vitro, in rat. The aim of our study was to verify the effect of the drug on 11 beta-OHSD activity in man at the doses currently used in clinical practice. We tested the activity of 11 beta-OHSD following both acute and protracted administration of furosemide. In the acute study, the drug was administered at low (40 mg i.v. in bolo) and high doses (infusion of 10 mg/kg bw i.v for six hours); the protracted furosemide administration consisted in 50 mg/day for 20 days, by mouth. The ratios between the cortisol metabolites tetrahydrocortisol plus allo-tetrahydrocortisol to tetra-hydrocortisone and urinary free cortisol to urinary free cortisone were used to measure the activity of 11 beta-OHSD. Urinary cortisol, cortisone and their metabolites were tested by a gas-chromatographic/mass spectrometric method. Neither acute nor prolonged administration of furosemide did affect the activity of 11 beta-OHSD although the drug was able to modify plasma aldosterone and PRA secretion and to determine hypokalemia. Our results suggest that furosemide does not play a significant role in 11 beta-OHSD modulation in humans, at least at the dosage used in clinical practice.
Document Type: article in journal/newspaper
File Description: STAMPA
Language: English
Relation: info:eu-repo/semantics/altIdentifier/pmid/12373630; info:eu-repo/semantics/altIdentifier/wos/WOS:000178698900003; volume:110; firstpage:272; lastpage:276; numberofpages:5; journal:EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES; https://hdl.handle.net/11577/2470625
DOI: 10.1055/s-2002-34589
Availability: https://hdl.handle.net/11577/2470625; https://doi.org/10.1055/s-2002-34589
Accession Number: edsbas.CA04C6B2
Database: BASE