1. The interrelationship between extracellular fluid volume and extracellular anion composition as determinants of sodium excretion was studied in thirty-four dogs. In six, hypovolaemia, hypochloraemia and hyperbicarbonataemia were induced by the administration of ethacrynic acid and a low chloride diet. Isotonic sodium bicarbonate was then infused resulting in a progressive increase in sodium excretion. After 3 h while continuing the sodium bicarbonate infusion, an infusion of hydrochloric acid was given in order to return extracellular anion composition towards normal. This resulted in a prompt fall in sodium excretion without a change in GFR.
2. Ten studies were performed to determine whether this hydrochloric acid-induced enhancement of sodium conservation depends upon the presence of volume depletion and sodium avidity or whether it could also be demonstrated under circumstances of volume expansion. In these studies, hypervolaemia, hypochloraemia, hyperbicarbonataemia and a brisk natriuresis were induced by infusing isotonic sodium bicarbonate into normal dogs. The addition of hydrochloric acid returned anion composition to normal and, as before, resulted in a prompt suppression of sodium excretion despite continued sodium loading and enhanced glomerular filtration.
3. Results obtained from three related protocols (six animals each) confirmed that hypochloraemia and hyperbicarbonataemia were the necessary prerequisite conditions for this effect of hydrochloric acid in volume expanded animals. We interpret these findings as evidence that the response of the kidney to changes in extracellular fluid volume may be significantly affected by changes in the extracellular concentration of physiologic anions.