A POSSIBLE MOLECULAR-BASIS OF NATRIURESIS DURING ISCHEMIC-REPERFUSIONINJURY IN THE KIDNEY

Ischemic renal injury is associated with increased fractional excretio n of sodium, suggesting a Na+ reabsorption deficiency in renal tubules . To determine whether alterations in expression of the major Na+ tran sporter genes might contribute to the natriuresis that follows ischemi c acute renal failure, the expression of these genes was analyzed in r enal cortex and medulla after ischemic-reperfusion injury. Rats were s ubjected to 30 min of renal pedicle clamping and then sacrificed at 12 , 24, or 48 h after reperfusion. Serum creatinine increased significan tly at 12 and 24 h, indicative of acute renal failure, but decreased s ubstantially by 48 h. mRNA levels for the NHE-3 Na/H exchanger of the proximal tubule, the apical Na-K-2Cl cotransporter of the thick ascend ing limb of Henle, the Na-CI cotransporter oi. the distal convoluted t ubule, the epithelial Na+ channel of the collecting duct, and the baso lateral Na+-K+-ATPase were measured by Northern hybridization. NHE-3 m RNA decreased by approximately 75% at 12 h and remained suppressed at 24 and 48 h after reperfusion. Na-K-2Cl cotransporter mRNA decreased b y approximately 88% at 12 h and remained suppressed at 24 and 48 h. Na -CI cotransporter mRNA remained unchanged at 12 h, decreased by approx imately 60% at 24 h, and returned to almost control levels at 48 h. mR NA levels for sodium channels (beta subunit) remained unchanged. Na+-K +-ATPase mRNA in the medulla decreased by approximately 35 to 40% at 1 2 and 24 h and by 70% at 48 h, whereas in cortex it decreased by only <15% at 12 or 48 h after reperfusion. These results suggest that sharp reductions in expression of the NHE-3 Na/H exchanger and the apical N a-K-2Cl cotransporter are major factors in the natriuresis/diuresis th at is one of the hallmarks of ischemic acute renal failure. Lasting su ppression of these transporters, despite improvement in renal function , could contribute to the deranged NaCl and water excretion that often leads to volume depletion during recovery from ischemic acute renal f ailure.