Digoxin was infused into a dog renal artery, using the contralateral kidney as control. At peak diuretic effect, sodium, potassium-adenosine triphosphatase (Na+,K+-ATPase) activity of both experimental cortex and medulla was significantly depressed compared to control. The inhibitory effect in vitro of ouabain on the control Na+,K+-ATPase from both medulla and cortex was time dependent; no regional difference in sensitivity was noted. The binding in vitro of 3H-ouabain to Na+, K+-ATPase from both experimental cortex and experimental medulla was significantly lower than that for control enzymes, suggesting previous occupation of drug-binding sites. The data represent further indication that digoxin-induced diuresis is related to inhibition of Na+,K+-ATPase.
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