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.