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Am J Physiol Renal Physiol 278: F925-F939, 2000;
0363-6127/00 $5.00
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Vol. 278, Issue 6, F925-F939, June 2000

Decreased abundance of major Na+ transporters in kidneys of rats with ischemia-induced acute renal failure

Tae-Hwan Kwon1, Jørgen Frøkiær2, Jin Suk Han3, Mark A. Knepper4, and Søren Nielsen1

1 Department of Cell Biology, Institute of Anatomy, University of Aarhus, DK-8000 Aarhus C; 2 Department of Clinical Physiology, Aarhus University Hospital and Institute of Experimental Clinical Research, DK-8200 Aarhus N, Denmark; 3 Department of Internal Medicine, Seoul National University Hospital, 110-744 Seoul, Korea; and 4 Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892

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 (UNaV) 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-Pi 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 (FENa) was significantly increased in mild ARF (30 min) and UNaV 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, FENa 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 FENa 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.

sodium transport; sodium-hydrogen exchanger; sodium-inorganic phosphate cotransporter; sodium-potassium-2 chloride transporter; sodium-chloride cotransporter


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