Effect of potassium deficiency on action of chlorothiazide in the rat

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Abstract
Chlorothiazide was administered to male rats which had been fed a potassium-deficient diet, and also to their pair-fed controls. Daily urine collections were carried out on the experimental and control rats before and during chlorothiazide administration. The drug caused a persistent increase in the daily urinary volume of the potassium-deficient rats, but only a transitory increase in the control rats. The striking increase in the daily urinary volume of the potassium-deficient rats was unaccompanied by an increase in solute output. The chlorothiazide did not affect the urinary-potassium loss in the potassium-deficient rats. No significant difference was found between the creatinine clearances of the potassium-deficient rats and their controls, nor did the creatinine clearances differ from those found in separate groups of potassium-deficient rats and controls to which chlorothiazide had not been administered. It is concluded that potassium deficiency does not interfere with the diuretic effect of chlorothiazide in the rat, but rather enhances it. The findings are consistent with the idea that chlorothiazide interferes with sodium reabsorption at a site proximal to that at which free water may be formed and at which complementary reabsorption of sodium takes place during the administration of chlorothiazide. An alternative explanation is that chlorothiazide may enhance the thirst of potassium-deficient rats.