Comparison of effects of acidosis and alkalosis on the renal action of Diamox

Abstract

Diamox was given to anesthetized hydropenic dogs by single intravenous injection in doses of 10–1000 mg/kg in order to establish a dosage-response pattern. Increments of urine bicarbonate excretion were 60 µm/min. after doses of 10 mg/kg, 400–500 µm/min. after doses of 100 mg/kg, 700–1000 µm/min. after doses of 300 mg/kg and 600–1180 µm/min. after doses of 500–1000 mg/kg. Urine flow was dependent predominantly on effective osmotic load, indicating that the diuretic action of Diamox did not affect the distal mechanism for water transport. Bicarbonate accounted for 30% of the urinary solutes. Alkalinizing effects of Diamox, similar to those of NaHCO₃, were found in dosages of over 300 mg/kg. Hence, the dosage used for evaluation of drug effect was restricted to the range 20–200 mg/kg. The action of Diamox was reduced to one half to one sixth of that expected when given to dogs under conditions of both metabolic and respiratory acidosis. For example, the increment of bicarbonate excretion was no more than 200 µm/min. after doses of 20–200 mg/kg. Such suppression of a drug action during acidosis was independent of glomerular clearance as well as of serum levels of HCO^–₃ and Na⁺. The action of Diamox under conditions of metabolic alkalosis or under normal conditions was greater than that observed under acidotic conditions. The relation of a postulated carrier-anhydrase molecule to Diamox inhibition under different conditions of plasma and urinary acidity is discussed.