1. In the rat dietary chloride restriction has been shown to cause an elevation of the plasma bicarbonate and urinary net acid excretion, provided dietary sodium is available. Likewise the degree of elevation of plasma bicarbonate during chloride depletion, produced by prior exposure to 8% CO2 for 24 hr, was dependent on whether sodium (as the neutral phosphate) was or was not being ingested.
2. Correction of the hypochloraemia and the elevated plasma bicarbonate following exposure to CO2 and subsequent recovery on a low chloride diet is more complete in the rat than the dog. Evidence is presented that the plasma chloride rises in the rat because of the movement of chloride out of intracellular sites, and that chloride depletion and/or the associated metabolic alkalosis elevates endogenous acid production.
3. Chloride depleted rats were re-exposed to 8% CO2 in air. Renal chloride conservation remained intact. The hypochloraemia and rise in plasma bicarbonate in response to CO2 were not dependent on chloruresis although urinary acid excretion and the rise in serum bicarbonate were inhibited when the plasma chloride did not fall.
4. Consideration of these experiments with the related micropuncture experiments of Warren et al. (1970) suggests that:
the intimate relationship between hypochloraemia and the elevation of plasma bicarbonate in respiratory acidosis is related to reciprocal changes in proximal tubular absorption of chloride and bicarbonate;
chloride depletion can increase bicarbonate absorption in the proximal tubule and urinary net acid excretion;
a rise in TF/P Cl in the proximal tubule does not necessarily correlate with changes in external chloride balance;
the distal chloride conserving mechanism is unaffected by rates of sodium or phosphate excretion, exposure to carbon dioxide, or increases in the rate of tubular bicarbonate absorption.