CHANGES IN EXPRESSION OF SODIUM COTRANSPORTERS AND AQUAPORIN-2 DURING ISCHEMIA-REPERFUSION INJURY IN RABBIT KIDNEY

Abstract

Ischemic renal injury is associated with defects in transport functions of the proximal tubules and urinary concentration ability. To determine whether alterations in expression of various transporter genes contribute to an impairment in renal functions, the expression of various solute transport genes was analyzed in renal cortex and medulla of rabbits with ischemic acute renal failure. Rabbits were subjected to 60 min of renal pedicle clamping followed by 24, 48, or 72 h of reperfusion. Urine volume and glomerular filtration rate were markedly decreased, which were accompanied by an increase in serum creatinine level and fraction Na⁺ excretion. Glucosuria and phosphaturia were evident during reperfusion periods. These alterations in renal functions were persisted to 72 h after reperfusion. The Na⁺-dependent uptakes of glucose and phosphate by brush border membrane vesicles were inhibited by 24 h of reperfusion. mRNA levels for Na⁺-glucose, Na⁺-phosphate, and Na⁺-succinate cotransporter analyzed by RT-PCR were not changed by 60 min of ischemia alone, but were significantly reduced by 24 h of reperfusion. mRNA levels for apical Na⁺-K⁺-2Cl⁻ cotransporter, NaCl cotransporter, and turea transporter in the medulla were not changed during reperfusion. Protein levels for AQP2 in the medulla, but not AQP1 in the cortex, analyzed by Western blot were significantly reduced at 24 h after reperfusion.

These results suggest that reductions in expression of Na⁺-cotransporter genes in the proximal tubules may be important factors in the impairment in Na⁺-dependent reabsorption of solutes and that decrease in AQP2 protein may be involved in defect in urinary concentration ability in rabbits with ischemic acute renal failure.

• Ischemia
• Reperfusion injury
• Expression
• Na⁺-dependent cotransporters
• Aquaporin
• Rabbit kidney