Bilateral ureteral obstruction downregulates expression of the
vasopressin sensitive aquaporin-2 water channel in rat kidney.
Frokiaer, Jorgen, David Marples, Mark A Knepper & Soren Nielsen.
Department of Clinical Physiology, Aarhus University Hospital and
Institute of Experimental Clinical Research, University of Aarhus;
Department of Cell Biology, Institute of Anatomy, University of
Aarhus, DK-8000 Aarhus C, Denmark; and Laboratory of Kidney and
Electrolyte Metabolism, National Heart, Lung and Blood Institute,
National Institutes of Healt, Bethesda, Maryland 20892.
APStracts 2:0205F, 1995.
Polyuria after release of bilateral ureteral obstruction (BUO) is
frequently seen in patients with urological disorders. In this study
we examined the effect of BUO, and release of BUO, on the expression
of the vasopressin-regulated water channel aquaporin-2 (AQP2) in rat
kidney. Ureters were obstructed for 24 hours in all experiments, and
BUO was either not released, or released for 24 hours, 48 hours or 7
days. Each group of experimental rats were matched with sham operated
controls. One kidney was used for membrane fractionation and
immunoblotting, whereas the contralateral was fixed for
immunocytochemistry. Immunoblotting demonstrated a significant
reduction in AQP2 expression in inner medulla during 24 hours of BUO
to 26 +/- 8 % (p<0.001). Release of BUO was associated with
immediate onset of a predominant osmotic dependent polyuria. Forty
eight hours after release of BUO, the reduction in AQP2 expression
persisted (19 +/- 8%, p<0.001), concurrent with a marked non
-osmotic postobstructive polyuria as determined by a significant
reduction in free water clearance (-50 +/- 7 vs. -85 +/- 10
[mu]l/min/kg, p < 0.05). Immunoflourescense and immunoelectron
microscopy confirmed the reduced levels of AQP2 in collecting duct
principal cells. Seven days after release, the renal excretion of
water and electrolytes had almost normalized. However, the
downregulation of AQP2 was only partly reversed (49 +/- 14 %,
p<0.001), and consistent with this the urinary concentrating
capacity was significantly reduced 7 days after release of BUO as
compared to sham operated rats in response to an 18 hours period of
thirst. This strongly suggests that the persistent down regulation of
AQP2 is the cause of the slow recovery in concentrating capacity. In
conclusion, BUO, and release of BUO, were associated with a marked
reduction in expression of AQP2, coincident with the development and
maintenance of postobstructive polyuria. Thus, reduced AQP2 levels
may represent an important factor in the slow recovery from
postobstructive diuresis.
Received 13 September 1995; accepted in final form 17 November
1995.
APS Manuscript Number F312-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 8 December 95