Decreased vasopressin-mediated renal water reabsorption in rats
with compensated liver cirrhosis.
Jonassen, Thomas E. N., S_ren Nielsen, Sten Christensen, and J_rgen
S_berg Petersen.
Department of Pharmacology, the Panum Institute, University of
Copenhagen, DK-2200, Denmark and Department of Cell Biology,
Institute of Anatomy, University of [angstrom]arhus, DK-8000,
Denmark
APStracts 5:0086F, 1998.
Experiments were performed to investigate vasopressin type-2 receptor
(V2) mediated renal water reabsorption and the renal expression of
the vasopressin-regulated water channel AQP-2 in cirrhotic rats with
sodium retention but without ascites. In addition, the expression of
the furosemide-sensitive type-1 Na-K-2Cl cotransporter (BSC-1) and
the natriuretic response to an i.v. test dose furosemide (7.5 mg/kg)
during acute V2-receptor blockade was measured. Acute V2-receptor
blockade with the selective non-peptide antagonist OPC-31260 (800
g/kg/h) was performed during conditions were volume depletion was
prevented by computer-driven, servo-controlled i.v. volume
replacement with 150 mM glucose. OPC-31260 produced a significantly
smaller increase in urine flow rate (-26%) and free water clearance
(-18%) in cirrhotic rats than in control rats. The natriuretic
response to an i.v. test dose furosemide (7.5 mg/kg) was
significantly increased in cirrhotic rats (+52%), but pretreatment
with OPC-31260 did not affect the natriuretic response to furosemide
in neither cirrhotic nor in control rats. Semi-quantitative
immunoblotting showed a significant downregulation of AQP-2 in the
renal cortex (-72%) and in the outer medulla (-44%).The relative
expression of of BSC-1 in the outer medulla was unchanged in CBL
rats. The cortico-papillary gradient of Na was significantly
increased in CBL rats. Since daily urine flow rate was similar in
cirrhotic and sham-operated rats, we suggest that non-vasopressin
-mediated water reabsorption is increased in cirrhotic rats probably
as a result of an increased cortico-medullary gradient due to
exaggerated NaCl reabsorption in the thick ascending limb of Henle_s
loop.
Received 1 December 1997; accepted in final form 23 April 1998.
APS Manuscript Number F376-7.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 8 May 1998