Sodium homeostasis is preserved in a global 11β-hydroxysteroid dehydrogenase type 1 knockout mouse model

Thorbjørn H Christensen, Matthew A Bailey, Christopher J Kenyon, Boye L Jensen, Robert W Hunter

Research output: Contribution to journalArticlepeer-review

Abstract

Glucocorticoids act in the kidney to regulate glomerular haemodynamics
and tubular sodium transport; the net effect favours sodium retention. 11β-
hydroxysteroid dehydrogenase type 1 (11βHSD1) is expressed in the renal tubules and the interstitial cells of the medulla, where it is likely to regenerate active glucocorticoids from inert 11-keto forms. The physiological function of renal 11βHSD1 is largely unknown. We hypothesised that loss of renal 11βHSD1 would result in salt wasting, and tested this in a knockout mouse model in which 11βHSD1 was deleted in all body tissues. In balance studies, 11βHSD1 deletion had no effect on water, sodium or potassium metabolism; transition to a low sodium diet did not reveal a natriuretic phenotype. Renal clearance studies demonstrated identical haemodynamic parameters (arterial blood pressure, renal blood flow, glomerular filtration rate) in knockout and wild-type mice, but revealed an augmented kaliuretic response to thiazides in 11βHSD1 knockouts. There was no effect on the natriuretic response to the amiloride analogue benzamil. Urinary excretion of deoxycorticosterone (DOC) Disclaimer: This is a confidential document. was higher in 11βHSD1 knockout mice and there was hypertrophy of cells in the zona fasciculata of the adrenal cortex. There was no difference in the activity of the reninangiotensin and nitric oxide systems, no difference in renal histology, and no difference in the abundance of key tubular transporter proteins. We conclude that any effect of 11βHSD1 on renal sodium excretion is subtle.
Original languageEnglish
Pages (from-to)1362-78
Number of pages17
JournalExperimental physiology
Volume100
Issue number11
Early online date3 Sep 2015
DOIs
Publication statusPublished - 2015

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