REDUCED NA-K-ATPASE IN DISTAL NEPHRON IN GLYCEROL-INDUCED ACUTE TUBULAR-NECROSIS

To further characterize changes in tubular Na-K-ATPase in acute tubular necrosis (ATN), segmental analysis was performed in rat nephrons. Na-K-ATPase was assayed in the following segments: proximal convolution (PC), proximal straight (PS), outer medullary thick ascending limb (MTAL), cortical thick ascending limb (CTAL), distal convolution (DC) and cortical collecting duct (CCD) in three groups of rats: 1.) intact; 2.) moderate non-oliguric ATN; and 3.) severe oliguric ATN. GFR and C(Na)/GFR x 100 were in group 1 0.80 ± 0.05 ml/min and 0.68 ± 0.06, in group 2 0.14 ± 0.02 and 1.46 ± 0.35, and in group 3 0.04 ± 0.01 and 0.46 ± 0.15, respectively. Na-K-ATPase in PC and PS were similar in all three groups. Na-K-ATPase levels were in MTAL: in group 1 37 ± 2 x 10-11 mol/mm/min, in group 2 20 ± 1 x 10-11, P < 0.001 versus group 1, and in group 3 24 ± 2 x 10-11, P < 0.001 versus group 1. In CTAL Na-K-ATPase levels were: in group 1 40 ± 2 x 10-11, in group 2 33 ± 1 x 10-11, P < 0.001 versus group 1, and in group 3 27 ± 2 x 10-11, P < 0.001 versus groups 1 and 2. In DC levels were: in group 1 43 ± 2 x 10-11, in group 2 33 ± 1 x 10-11, P < 0.001 versus group 1, and in group 3 22 ± 1 x 10-11, P < 0.001 versus groups 1 and 2. Levels in CCD were: in group 1 20 ± 1 x 10-11, in group 2 25 ± 1 x 10-11, P < 0.001 versus group 1, in group 3 24 ± 2 x 10-11, P < 0.05 versus group 1. Almost no differences were noticed in Mg-ATPase, suggesting specificity of the changes to Na-K-ATPase. These results show that Na-K-ATPase remains unchanged in PC and PS, is elevated in CCD, and is reduced in MTAL, CTAL and DC both in moderate and severe ATN. There is a direct relationship between the reduction of the enzymatic activity in the CTAL and DC and the severity of ATN. The present findings suggest that TAL and DC are the tubular sites of impaired Na transport in this model of ATN.