Losartan treatment normalizes renal sodium and water handling in rats with mild congestive heart failure.
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 V(2)-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 V(2)-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.
Staahltoft
Dennis
D
Department of Pharmacology, University of Copenhagen, DK-2200 Copenhagen N, Denmark.
Nielsen
Søren
S
Janjua
Nadeem R
NR
Christensen
Sten
S
Skøtt
Ole
O
Marcussen
Niels
N
Jonassen
Thomas E N
TE
D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D000959:Antihypertensive Agents / Q000494:pharmacology*; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins / Q000378:metabolism; D001552:Benzazepines / Q000494:pharmacology; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism; D007685:Kidney Tubules, Collecting / Q000378:metabolism; D008138:Loop of Henle / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017483:Receptors, Vasopressin / Q000378:metabolism; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000378:metabolism*; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism; D064466:Solute Carrier Family 12, Member 1; D014667:Vasopressins / Q000378:metabolism; D014867:Water / Q000378:metabolism*; D014882:Water-Electrolyte Balance / Q000187:drug effects
D065092:Antidiuretic Hormone Receptor Antagonists; D000959:Antihypertensive Agents; C496025:Aqp2 protein, rat; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins; D001552:Benzazepines; D017483:Receptors, Vasopressin; C578716:Slc12a1 protein, rat; D028021:Sodium-Potassium-Chloride Symporters; D064466:Solute Carrier Family 12, Member 1; D014867:Water; D014667:Vasopressins; C076251:mozavaptan; D012964:Sodium; D019808:Losartan