부산대학교 도서관

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.