Impaired aquaporin and urea transporter expression in rats with adriamycin-induced nephrotic syndrome.
Nephrotic syndrome is associated with abnormal regulation of renal water excretion. To investigate the role of collecting duct water channels and solute transporters in this process, we have carried out semiquantitative immunoblotting of kidney tissues from rats with adriamycin-induced nephrotic syndrome. These experiments demonstrated that adriamycin-induced nephrotic syndrome is associated with marked decreases in expression of aquaporin-2, aquaporin-3, aquaporin-4, and the vasopressin-regulated urea transporter in renal inner medulla, indicative of a suppression of the capacity for water and urea absorption by the inner medullary collecting duct. In contrast, expression of the alpha(1)-subunit of the Na,K-ATPase in the inner medulla was unaltered. Light and electron microscopy of perfusion-fixed kidneys demonstrated that the collecting ducts are morphologically normal and unobstructed. Inner medullary expression of the descending limb water channel, aquaporin-1, was not significantly altered, pointing to a selective effect on the collecting duct. Aquaporin-2 and aquaporin-3 expression was also markedly diminished in the renal cortex, indicating that the effect is not limited to the inner medullary collecting duct. Differential centrifugation studies and immunocytochemistry in inner medullary thin sections demonstrated increased targeting of aquaporin-2 to the plasma membrane, consistent with the expected short-term action of vasopressin on aquaporin-2 trafficking. The extensive down-regulation of aquaporin and urea transporter expression may represent an appropriate renal response to the extracellular volume expansion observed in nephrotic syndrome, but may occur at the expense of decreased urinary concentrating and diluting capacity.
Fernández-Llama
P
P
Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda Maryland, USA.
Andrews
P
P
Nielsen
S
S
Ecelbarger
C A
CA
Knepper
M A
MA
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D051398:Aquaporin 1; D051399:Aquaporin 2; D051400:Aquaporin 3; D051401:Aquaporin 4; D051403:Aquaporin 6; D020346:Aquaporins; D002352:Carrier Proteins / Q000378:metabolism*; D004317:Doxorubicin / Q000633:toxicity; D019204:GTP-Binding Proteins / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D007473:Ion Channels / Q000378:metabolism*; D007679:Kidney Medulla / Q000378:metabolism / Q000648:ultrastructure; D007685:Kidney Tubules, Collecting / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008854:Microscopy, Electron; D009404:Nephrotic Syndrome / Q000139:chemically induced / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014508:Urea / Q000378:metabolism; D000096982:Urea Transporters
D000262:Adenylyl Cyclases; D051398:Aquaporin 1; D051399:Aquaporin 2; D051400:Aquaporin 3; D051401:Aquaporin 4; D051403:Aquaporin 6; D020346:Aquaporins; D002352:Carrier Proteins; D004317:Doxorubicin; D019204:GTP-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; D007473:Ion Channels; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D014508:Urea; D000096982:Urea Transporters; C496022:Aqp1 protein, rat; C496025:Aqp2 protein, rat; C496029:Aqp3 protein, rat; C496032:Aqp4 protein, rat