Altered expression of Na transporters NHE-3, NaPi-II, Na-K-ATPase, BSC-1, and TSC in CRF rat kidneys.
In chronic renal failure (CRF), reduction in renal mass leads to an increase in the filtration rates of the remaining nephrons and increased excretion of sodium per nephron. To address the mechanisms involved in the increased sodium excretion, we determined the total kidney levels and the densities per nephron of the major renal NaCl transporters in rats with experimental CRF. Two weeks after 5/6 nephrectomy (reducing the total number of nephrons to approximately 24 +/- 8%), the rats were azotemic and displayed increased Na excretion. Semiquantitative immunoblotting revealed significant reduction in the total kidney levels of the proximal tubule Na transporters NHE-3 (48% of control), NaPi-II (13%), and Na-K-ATPase (30%). However, the densities per nephron of NHE-3, NaPi-II, and Na-K-ATPase were not significantly altered in remnant kidneys, despite the extensive hypertrophy of remaining nephrons. Immunocytochemistry confirmed the reduction in NHE-3 and Na-K-ATPase labeling densities in the proximal tubule. In contrast, there was no significant reduction in the total kidney levels of the thick ascending limb and distal convoluted tubule NaCl transporters BSC-1 and TSC, respectively. This corresponded to a 3.6 and 2.5-fold increase in densities per nephron, respectively (confirmed by immunocytochemistry). In conclusion, in this rat CRF model: 1) increased fractional sodium excretion is associated with altered expression of proximal tubule Na transporter expression (NHE-3, NaPi-II, and Na-K-ATPase), consistent with glomerulotubular imbalance in the face of increased single-nephron glomerular filtration rate; and 2) compensatory increases in BSC-1 and TSC expression per nephron occur in distal segments.
Kwon
T H
TH
Department of Cell Biology, Institute of Anatomy, University of Aarhus, DK-8000 Aarhus, Denmark.
Frøkiaer
J
J
Fernández-Llama
P
P
Maunsbach
A B
AB
Knepper
M A
MA
Nielsen
S
S
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D004231:Diuresis; D007668:Kidney / Q000378:metabolism*; D007671:Kidney Concentrating Ability; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000503:physiopathology; D009088:Mucoproteins / Q000378:metabolism; D009318:Natriuresis; D009392:Nephrectomy / Q000379:methods; D051381:Rats; D011919:Rats, Inbred Strains; D011955:Receptors, Drug / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D049992:Sodium Chloride Symporters; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D050608:Sodium-Phosphate Cotransporter Proteins; D028021:Sodium-Potassium-Chloride Symporters; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters; D058949:Uromodulin
D002352:Carrier Proteins; D009088:Mucoproteins; D011955:Receptors, Drug; C578876:Slc12a3 protein, rat; C000613387:Slc9a3 protein, rat; D049992:Sodium Chloride Symporters; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D050608:Sodium-Phosphate Cotransporter Proteins; D028021:Sodium-Potassium-Chloride Symporters; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters; C548614:Umod protein, rat; D058949:Uromodulin; C064415:thiazide receptor; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase