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Am J Physiol Renal Physiol 282: F307-F315, 2002; doi:10.1152/ajprenal.00132.2001
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Vol. 282, Issue 2, F307-F315, February 2002

Losartan treatment normalizes renal sodium and water handling in rats with mild congestive heart failure

Dennis Staahltoft1, Søren Nielsen2, Nadeem R. Janjua1, Sten Christensen1, Ole Skøtt3, Niels Marcussen4, and Thomas E. N. Jonassen1

1 Department of Pharmacology, University of Copenhagen, DK-2200 Copenhagen N; 2 Department of Cell Biology, Institute of Anatomy, University of Aarhus, and 4 University Institute of Pathology, Aarhus Kommunehospital, DK-8000 Aarhus C; and 3 Department of Physiology and Pharmacology, University of Southern Denmark, DK-5000 Odense C, Denmark

This study was designed to examine the effect of losartan treatment on renal tubular function in rats with mild congestive heart failure (CHF) induced by ligation of the left anterior descending artery. In rats with CHF, there was a significant decrease in daily sodium excretion, which caused sodium retention relative to control rats. Renal function studies revealed that glomerular filtration rate and proximal tubular sodium handling were normal. However, expression of the Na+-K+-2Cl- cotransporter (NKCC2) in the thick ascending limb of Henle's loop was increased. Moreover, vasopressin-mediated renal water reabsorption, as evaluated by the aquaretic response to selective V2-receptor blockade, was significantly increased. Losartan treatment normalized expression of NKCC2 and decreased expression of the vasopressin-regulated water channel aquaporin-2. This was associated with normalization of daily sodium excretion and normalization of the aquaretic response to V2-receptor blockade. Together, these results indicate that, in rats with CHF, losartan treatment inhibits increased sodium reabsorption through NKCC2 in the thick ascending limb of Henle's loop and water reabsorption through aquaporin-2 in the collecting ducts, which may be involved in improving renal function in losartan-treated CHF rats.

aquaporin-2; sodium-potassium-2 chloride cotransporter; vasopressin; thick ascending limb; collecting ducts


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