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

Area of Science:

• Endocrinology
• Pharmacology

Background:

• Mineralocorticoid receptors bind aldosterone and cortisol equally.
• 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) enzyme converts cortisol to cortisone, enabling aldosterone's preferential binding.
• Inhibition of 11 beta-OHSD causes apparent mineralocorticoid excess (AME) syndrome.

Purpose of the Study:

• To investigate the effect of furosemide on 11 beta-OHSD activity in humans.
• To determine if furosemide, at clinically relevant doses, modulates 11 beta-OHSD activity.

Main Methods:

• Human subjects received acute (low and high dose) or protracted (20 days) furosemide administration.
• 11 beta-OHSD activity was assessed by measuring urinary cortisol and cortisone metabolites using gas-chromatography/mass spectrometry.
• Ratios of cortisol metabolites (tetrahydrocortisol/allo-tetrahydrocortisol to tetra-hydrocortisone) and urinary free cortisol to cortisone were analyzed.

Main Results:

• Furosemide administration, both acute and prolonged, did not alter 11 beta-OHSD activity in humans.
• Furosemide did affect plasma aldosterone and renin-angiotensin-aldosterone system (PRA) secretion and induced hypokalemia.
• No significant role for furosemide in 11 beta-OHSD modulation was observed at tested clinical dosages.

Conclusions:

• Furosemide does not appear to significantly inhibit 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) activity in humans at doses used in clinical practice.
• Despite altering aldosterone and electrolyte balance, furosemide's effect is not mediated through 11 beta-OHSD inhibition.