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Effects of acetazolamide on proximal tubule chloride potassium and bi carbonate transport in normal and acidotic dogs during distal blockade

, : Effects of acetazolamide on proximal tubule chloride potassium and bi carbonate transport in normal and acidotic dogs during distal blockade. Journal of Clinical Investigation 60(1): 162-170

The establishment of a tubular fluid to plasma Cl gradient in the late proximal tubule by the reabsorption of HCO3- (and other anions) in the early proximal tubule may be responsible for a significant part of NaCl and water reabsorption in the proximal tubule. The effects of acetazolamide on proximal tubule water and electrolyte excretion were examined in 6 normal dogs and 10 chronic NH4Cl loaded dogs during distal blockade produced by ethacrynic acid and chlorothiazide administration. During distal blockade control urine/plasma osmolality and urine/plasma Na were close to unity in all experiments. Urine/plasma Cl and urine/plasma HCO3- were 1.21 .+-. 0.02 and 0.75 .+-. 0.07 in normal and 1.24 .+-. 0.01 and 0.04 .+-. 0.01 in acidotic dogs, respectively. After administration of acetazolamide (20 mg/kg i.v.), there was a significant increase in urine flow, absolute and fractional excretion of Na, HCO3- and Cl in all animals. Associated with these effects, urine/plasma osmolality and urine/plasma Na remained unchanged, but urine/plasma Cl decreased significantly to 1.15 .+-. 0.01 in normal and to 1.19 .+-. 0.01 in acidotic dogs. In acidotic dogs there was a significant correlation between increase in HCO3-, Na or Cl excretion after acetazolamide and the plasma HCO3- level (range 6.8-12.5 meq/l). A significant effect of acetazolamide on HCO3-, Na and Cl reabsorption in the proximal tubule, even in the face of severe acidosis, are demonstrated. The decrease in Cl reabsorption (and accompanying Na) after acetazolamide is related to the decrease in HCO3- reabsorption and the associated decrease in the transtubular Cl gradient.


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