NA PUMP DEFECTS IN CHRONIC UREMIA CANNOT BE ATTRIBUTED TO CHANGES IN NA-K-ATPASE MESSENGER-RNA OR PROTEIN

We have found abnormalities in Na-K-adenosinetriphosphatase (Na-K-ATPa se) function in different tissues of rats with chronic renal failure ( CRF). A potential mechanism for these findings is a change in Na-K-ATP ase alpha- and/or beta-gene expression. To evaluate this possibility, we compared CRF with pair-fed, sham-operated rats to determine whether chronic uremia changes the expression of Na-K-ATPase alpha(1)-, alpha (2)-, beta(1)-, and beta(2)-isoform mRNAs or protein in different type s of skeletal muscle, heart, liver, adipose, and kidney tissue. In CRF rats, alpha(1)-mRNA in heart tended to be higher and beta(2)-mRNA was lower in fat and kidney. There were no other statistically significan t differences in isoform mRNAs in tissues of CRF compared with the con trol rats. Western blot analysis revealed a 38% increase in alpha(1)-p rotein in adipocytes and a 61% decrease in kidney of CRF rats but no s ignificant differences in the amounts of isoform protein in other tiss ues. Thus, in uremia, posttranslational events or inhibitors of the en zyme are more likely causes of defects in Na-K-ATPase than changes in mRNA or protein abundance.