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 s ignificant impairment of tubular Na reabsorption. We examined whether tempo rary bilateral renal ischemia (30, 40, or 60 min) and reperfusion (1-5 days ) affect the abundance of several renal Na transporters and urinary Na excr etion (UNaV) in rats. In rats with mild ARF (30 min), immunoblotting reveal ed 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 signif icant decrease in type 1 bumetanide-sensitive cotransporter (BSC-1) and thi azide-sensitive cotransporter (TSC) levels. Consistent with reduced Na tran sporter abundance, fractional urinary Na excretion (FENa) was significantly increased in mild ARF (30 min) and UNaV was unchanged, despite a marked re duction in glomerular filtration rate. Na transporter levels and renal Na h andling were normalized within 5 days. Severe ischemic injury (60 min) resu lted 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 signi ficantly increased at days 1 and 5. Intravenous K-melanocyte-stimulated hor mone treatment partially prevented the ischemia-induced downregulation of r enal Na transporters and reduced the high FENa to control levels. We conclu de that reduced levels of Na transporters along the nephron may play a crit ical role in the impairment of tubular Na reabsorption, and hence increased Na excretion, in ischemia-induced ARF.