RT Journal Article
SR Electronic
T1 INTERACTIONS OF DIGOXIN AND ETHACRYNIC ACID WITH RENAL SODIUM-POTASSIUM-ACTIVATED ADENOSINE TRIPHOSPHATASE
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 605
OP 614
VO 188
IS 3
A1 Martinez-Maldonado, Manuel
A1 Tsaparas, N.
A1 Inagaki, C.
A1 Schwartz, A.
YR 1974
UL http://jpet.aspetjournals.org/content/188/3/605.abstract
AB The effects of intravenous ethacrynic acid (EA) , 5 mg/kg b.wt., on renal electrolyte excretion was examined in two groups of dogs. Group I (seven dogs) received EA 60 minutes after the infusion of 0.7 µg/kg/min of digoxin into one renal artery. In group II (seven dogs), digoxin (4.0 µg/kg/min) was infused into one renal artery for 60 minutes; EA was administered 30 minutes after commencing the infusion. In both groups digoxin always led to a significant rise in urine flow (V), absolute (UNaV) and fractional sodium excretion (FENa) and osmolar clearance (COSM) in the infused kidney. In group I dogs, EA led to a rise in V, UNaV, FENa and COSM bilaterally; these values were significantly greater in the digoxin-infused kidneys. Free water reabsorption (TCH2O) was equally depressed in both kidneys in this group. In group II, EA also resulted in a higher increase in V, UNaV, FENa and COSM in the digoxin-infused kidney. On the other hand, TCH2O tended to fall more in the control than in the digoxin-infused kidney. Comparison of the changes in TCH2O, V and FENa in control and digoxin-infused kidneys suggest that, although EA can potentiate the inhibitory effect of digoxin on renal sodium reabsorption, its effects are partially blocked by the cardiac glycoside. The apparent differences in TCH2O suggest that the major site of interaction of the two drugs may be the ascending limb of Henle's loop. Isolation of cortical and medullary sodium-potassium-activated adenosine triphosphatase (Na+,K+-ATPase) demonstrated that enzyme activity was depressed by digoxin and that, in vivo, EA did not reduce the activity further. In vitro, however, addition of EA to the enzyme already inhibited by digoxin reduced activity further. This effect was nonspecific since it also depressed ouabain-insensitive ATPase. The present results and the nonspecific inhibition of NA+, K+-ATPase by EA make it unlikely that its action characterizes a specific ion "pump." © 1974 by The Williams & Wilkins Co.