Contraction alkalosis in the awake rat: Study of its generation and 24-hour follow-up

Abstract

Contraction alkalosis in awake rat: Study of its generation and 24-hour follow-up. Two groups of awake rats were used to study the role played by the of extracellular water (ECW) in the generation of alkalosis following an i.v. injection of furose-mide, 25 mg/kg -1 of body wt. In the first group, iterative sampling was performed until the 5th hour after the injection. In the second group, the first sample was drawn at the 5th hour. ECW contracted by 19% 2 hours after the furosemide injection in group 1 and by 25% 5 hours after the injection in group 2. During the same periods, plasma bicarbonate concentration (P HCO 3 ) increased by 4.1 and 2.7 mmoles · liter -1 in groups 1 and 2, respectively. This was far below the theoretical increase (6.1 and 8.0 mmoles · liter -1 ) calculated from the degree of ECW contraction. Simultaneously, arterial PCO 2 rose by 4 mm Hg (group 1) and 2 mm Hg (group 2), and the ΔPCO 2 /ΔP HCO 3 ratio was 0.97 and 0.74 mm Hg per mmole for groups 1 and 2, respectively. Arterial blood pH increased by only 0.02 U in both groups. Net hydrogen ion excretion rate did not change. The urinary excretion rate of both bicarbonate and titratable acidity (TA) significantly increased, whereas the ammonium excretion rate and urinary pH were not modified. From the 5th to the 22nd or the 24th hour, P HCO 3 and arterial PCO 2 progressively decreased, despite a persistent and an increased net urinary hydrogen ion excretion, with a greater TA excretion and a lower urinary pH than controls had. We found that the alkalosis occurring during the first 5 hours was a pure contraction alkalosis, since the hydrogen ion balance was not altered. Furosemide inhibition of carbonic anhydrase could explain the enhancement of the rate of bicarbonate excretion. The increase in the rate of TA excretion could be caused by a rise of both urinary phosphate excretion and distal hydrogen ion secretion. The increase in P HCO 3 was mitigated by a large net bicarbonate transfer into cells, as high as 12% (group 1) and 21% (group 2) of the initial extracellular store. It was significantly correlated to the degree of ECW contraction. From the 5th to the 24th hour, the rise of net urinary hydrogen ion excretion was presumably linked to the increased excretion of phosphates and other poorly reabsorbable anions retained in plasma during the acute phase of contraction. A persistent shift of bicarbonate into cells might account for the fall in bicarbonate concentration occurring during this period.