COMT KNOCK-OUT MICE SHOW REDUCED RENAL SODIUM EXCRETION AFTER VOLUME EXPANSION
Research field:Kidney physiology
Authors:Odlind C, Männistö P T, Reenilä I, Gogos J A, Karayiorgou M, Hansell P
Address of presenting
author:		Cecilia Odlind
Dept of Physiology
Uppsala University
Biomedical center
Box 572
S-751 23 Uppsala
Sweden
E-mail:cecilia.odlind@fysiologi.uu.se
Phone:+46-18-4714407
Fax:+46-18-4714938
Text of abstract Introduction
Dopamine (DA) is an intrarenal natriuretic hormone involved in sodium homeostasis. DA metabolism is catalysed by the enzymes catechol-O-methyl transferase (COMT) and monoamine oxidase (MAO). We have previously shown that inhibition of COMT using entacapone results in a potent natriuretic response mediated mainly via the D1-like receptor (Odlind et al. 1999) while MAO inhibition using phenelzine does not alter sodium excretion. The present study was performed in anaesthetized wild-type mice, COMT knock-out (KO) mice and normal rats to further investigate the importance of COMT in DA mediated natriuresis.

Methods
The mice were anaesthetized with isoflurane, catheterized and after 60 minutes control sampling the mice (wild type, heterozygote or homozygote) were volume expanded with isotonic saline (5 % of bw) and were followed for 4x30 minutes. The rats were anaesthetized with inactin, catheterized and after stabilization the rats were volume expanded with isotonic saline (5 % of bw) and were then followed for 30 min. The kidneys were removed and sliced for measurements of COMT and MAO activity.

Results
In the homozygous COMT KO mice the natriuretic response to isotonic sodium loading was only 40% of that in the wild-type mice. In normal rats isotonic sodium loading results in a partly D1-like receptor mediated natriuresis. Renal cortical COMT activity is reduced by 13% while no change occur in cortical MAO-A or B activity.

Conclusions
COMT KO mice have a reduced ability to excrete an isotonic sodium load. Furthermore, rat renal cortical COMT activity is reduced during partly D1-like receptor-dependent natriuresis following isotonic sodium loading, whereas MAO activity remains unchanged. These results strengthens our suggestion that COMT has an important role in regulating dopamine mediated natriuresis.

References
Odlind C, Göransson V & Hansell P.
Experimental Nephrology 1999; 7:314-322

Keywords:COMT, mice, sodium, dopamine, natriuresis

Created 2000-05-02