EXPERIMENTAL RENAL-FAILURE IN THE RAT MODULATES CARDIAC NA,K-ATPASE ALPHA-2 MESSENGER-RNA BUT NOT PROTEIN

The decreased abundance and enzymatic activity of myocardial Na,K-ATPa se have been recognized previously to occur in chronic uremia. However , the activity of the cardiac sodium pump as defined by the uptake of Rb-86 is normal. The discrepancies between these findings may have res ulted from the inability to distinguish between the different Na,K-ATP ase isoforms now known to exist in cardiac muscle, To investigate this question, steady-state levels of Na,K-ATPase alpha and beta mRNA isof orms, alpha1, alpha2, and beta1 protein, and specific high-affinity bi nding of (H-3)ouabain were quantitated in cardiac muscle from uremic a nd pair-fed, sham-operated control rats. Steady-state levels Of alpha2 and beta2 mRNA were significantly decreased (percentage of control le vels: alpha2, 48 +/- 10; beta2, 74 +/- 9; N = 10; P < 0.025) in chroni c renal failure without ony change in alpha1, alpha3, or beta1 express ion. The number of high-affinity (H-3)ouabain-binding sites and Na,K-A TPase alpha1, alpha2, and beta1 subunits was not different from contro l. In acute renal failure, alpha2 and beta2 mRNA levels also were sign ificantly decreased (percentage of control levels: alpha2, 24 +/- 5; b eta2, 44 +/- 8; N = 6; P < 0.001), but there was no change in the leve l of alpha3 or beta1 mRNA, the number of high-affinity (H-3) ouabain-b inding sites, or the level of Na,K-ATPase alpha2 and beta1 subunits. a lpha1 mRNA and subunit levels were increased by 44% (0.05 < P < 0.10) and 30% (P < 0.025), respectively. Acute and chronic uremia affects so dium pump biosynthesis at multiple levels. These findings suggest that the previously reported decrease in cardiac Na,K-ATPase activity in c hronic uremia was not the result of a decrease in pump number.