Experimental renal failure in the rat modulates cardiac Na,K-ATPase alpha 2 mRNA but not protein.
The decreased abundance and enzymatic activity of myocardial Na,K-ATPase have been recognized previously to occur in chronic uremia. However, the activity of the cardiac sodium pump as defined by the uptake of 86Rb is normal. The discrepancies between these findings may have resulted from the inability to distinguish between the different Na,K-ATPase isoforms now known to exist in cardiac muscle. To investigate this question, steady-state levels of Na,K-ATPase alpha and beta mRNA isoforms, alpha 1, alpha 2, and beta 1 protein, and specific high-affinity binding of [3H]ouabain were quantitated in cardiac muscle from uremic and pair-fed, sham-operated control rats. Steady-state levels of alpha 2 and beta 2 mRNA were significantly decreased (percentage of control levels: alpha 2, 48 +/- 10; beta 2, 74 +/- 9; N = 10; P < 0.025) in chronic renal failure without any change in alpha 1, alpha 3, or beta 1 expression. The number of high-affinity [3H]ouabain-binding sites and Na,K-ATPase alpha 1, alpha 2, and beta 1 subunits was not different from control. In acute renal failure, alpha 2 and beta 2 mRNA levels also were significantly decreased (percentage of control levels: alpha 2, 24 +/- 5; beta 2, 44 +/- 8; N = 6; P < 0.001), but there was no change in the level of alpha 3 or beta 1 mRNA, the number of high-affinity [3H]ouabain-binding sites, or the level of Na,K-ATPase alpha 2 and beta 1 subunits.(ABSTRACT TRUNCATED AT 250 WORDS)
da Silva
J C
JC
Department of Medicine, New England Medical Center, Boston, MA 02111.
Shi
X J
XJ
Johns
C A
CA
Jefferson
D M
DM
Grubman
S A
SA
Madias
N E
NE
Perrone
R D
RD
D058186:Acute Kidney Injury / Q000150:complications; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D015152:Blotting, Northern; D015153:Blotting, Western; D015971:Gene Expression Regulation, Enzymologic; D006977:Hypertension, Renal / Q000188:drug therapy / Q000201:enzymology; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D007676:Kidney Failure, Chronic / Q000150:complications; D008297:Male; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000235:genetics; D009132:Muscles / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology*; D010042:Ouabain / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012413:Rubidium; D000254:Sodium-Potassium-Exchanging ATPase / Q000096:biosynthesis* / Q000235:genetics; D014511:Uremia / Q000201:enzymology* / Q000209:etiology
D000959:Antihypertensive Agents; D007527:Isoenzymes; D009124:Muscle Proteins; D012333:RNA, Messenger; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D012413:Rubidium