Decreased abundance of major Na(+) transporters in kidneys of rats with ischemia-induced acute renal failure.
Ischemia-induced acute renal failure (ARF) is known to be associated with significant impairment of tubular Na reabsorption. We examined whether temporary bilateral renal ischemia (30, 40, or 60 min) and reperfusion (1-5 days) affect the abundance of several renal Na transporters and urinary Na excretion (U(Na)V) in rats. In rats with mild ARF (30 min), immunoblotting revealed that proximal tubule type 3 Na(+)/H(+) exchanger (NHE-3) and type II Na-P(i) cotransporter (NaPi-II) were significantly decreased to 28 +/- 6 and 14 +/- 6% of sham levels, respectively, at day 1. Moreover, Na(+)-K(+)-ATPase levels were also significantly decreased (51 +/- 11%), whereas there was no significant decrease in type 1 bumetanide-sensitive cotransporter (BSC-1) and thiazide-sensitive cotransporter (TSC) levels. Consistent with reduced Na transporter abundance, fractional urinary Na excretion (FE(Na)) was significantly increased in mild ARF (30 min) and U(Na)V was unchanged, despite a marked reduction in glomerular filtration rate. Na transporter levels and renal Na handling were normalized within 5 days. Severe ischemic injury (60 min) resulted in a marked decrease in the abundance of Na(+)-K(+)-ATPase, NHE-3, NaPi-II, BSC-1, and TSC at both days 1 and 5. Consistent with this, FE(Na) was significantly increased at days 1 and 5. Intravenous K-melanocyte-stimulated hormone treatment partially prevented the ischemia-induced downregulation of renal Na transporters and reduced the high FE(Na) to control levels. We conclude that reduced levels of Na transporters along the nephron may play a critical role in the impairment of tubular Na reabsorption, and hence increased Na excretion, in ischemia-induced ARF.
Kwon
T H
TH
Department of Cell Biology, Institute of Anatomy, University of Aarhus, Denmark.
Frøkiaer
J
J
Han
J S
JS
Knepper
M A
MA
Nielsen
S
S
D058186:Acute Kidney Injury / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D004231:Diuresis; D058973:Folate Receptors, GPI-Anchored; D026541:Heymann Nephritis Antigenic Complex; D007150:Immunohistochemistry; D017136:Ion Transport; D007511:Ischemia / Q000150:complications; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D009318:Natriuresis; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface; D011955:Receptors, Drug / Q000378:metabolism; D015427:Reperfusion Injury / Q000150:complications / Q000378:metabolism / Q000517:prevention & control; D012964:Sodium / Q000378:metabolism*; D049992:Sodium Chloride Symporters; D027982:Sodium-Bicarbonate Symporters; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics / Q000378:metabolism; D050608:Sodium-Phosphate Cotransporter Proteins; D050609:Sodium-Phosphate Cotransporter Proteins, Type I; D050610:Sodium-Phosphate Cotransporter Proteins, Type II; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters; D000521:alpha-MSH / Q000494:pharmacology
D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D026541:Heymann Nephritis Antigenic Complex; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; D011955:Receptors, Drug; C578876:Slc12a3 protein, rat; C498902:Slc4a7 protein, rat; C000613387:Slc9a3 protein, rat; D049992:Sodium Chloride Symporters; D027982:Sodium-Bicarbonate Symporters; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D050608:Sodium-Phosphate Cotransporter Proteins; D050609:Sodium-Phosphate Cotransporter Proteins, Type I; D050610:Sodium-Phosphate Cotransporter Proteins, Type II; D064486:Solute Carrier Family 12, Member 3; D027981:Symporters; C064415:thiazide receptor; D000521:alpha-MSH; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase