Effect of Na?K-ATPase inhibition on hydrogen ion and potassium secretion

The purpose of the present study was to examine whether in vivo inhibition of renal Na–K-ATPase affects renal H⁺ and potassium (K) secretion. Infusion of digoxin, furosemide, or ethacrynic acid into one renal artery of HCO₃ loaded dogs caused similar increases in urine flow, fractional Na and Cl excretion, and fractional water excretion. Glomerular filtration rate and urinary HCO₃ concentration fell comparably in all experiments. Maximal HCO₃ reabsorption was not depressed by any of the drugs infused, however only digoxin inhibited renal Na–K-ATPase activity. Furthermore, unilateral digoxin infusion resulted in a marked depression in the urine to bloodpCO₂ gradient (U-BpCO₂) and prevented the rise in fractional K excretion secondary to HCO₃ infusion observed in the contralateral control kidney. At all urinary HCO₃ concentrations, U-BpCO₂ was significantly higher in urine obtained from furosemide or ethacrynic acid infused kidneys than in urine obtained from digoxin infused kidneys. In addition, furosemide or ethacrynic acid administration markedly enhanced fractional K excretion in both kidneys. The systemic infusion of tris(hydroxymethyl)aminomethane (THAM; pK 8.0) failed to return U-BpCO₂ in the digoxin infused experimental kidneys to control levels, whereas THAM caused a marked rise in U-BpCO₂ in the control kidney. These data demonstrate that the in vivo inhibition of renal Na–K-ATPase by digoxin causes a defect in the secretion of both H⁺ and K. This defect likely results from the dissipation of the Na dependent lumen negative potential difference (PD) by digoxin, since a lumen negative PD favors both H⁺ and K secretion in the collecting duct. Furthermore, these data do not support the notion that furosemide or ethacrynic acid affect tubular transport through the inhibition of renal Na–K-ATPase activity.