The effect of chlorothiazide on renal excretion of electrolytes and free water

Abstract

Chlorothiazide was given intravenously to a group of normal human subjects and to one patient with diabetes insipidus, and its effects on renal function were compared with those of meralluride administered under similar circumstances. Following the administration of chlorothiazide, the urine flow and solute output increased but the free water clearance did not increase. Administration of meralluride was followed by a comparable increase in urine flow, a lesser rise in solute output, and an increased excretion of free water. Chlorothiazide produced a considerably greater increase in solute (sodium chloride) excretion than did meralluride. This difference was particularly evident in a sodium-depleted subject. The natriuretic effects of Chlorothiazide occurred despite an average reduction in the glomerular filtration rate of 16.9 per cent. Chlorothiazide also promoted the excretion of potassium, whereas meralluride had little effect on potassium excretion. When given together, the response to meralluride and chlorothiazide appeared to be additive in respect to total solute excretion. However, the potassium diuresis of chlorothiazide was prevented by previous administration of a mercurial agent. The findings perhaps suggest the presence of more than one renal transport mechanism concerned with the reabsorption of strong monovalent electrolytes. The observations can be explained by the hypothesis that meralluride acts only in the proximal tubule, while chlorothiazide affects solute (sodium and chloride) reabsorption both in the proximal and in the distal segments of the nephron.