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Effect of Chlorothiazide on Water Consumption in the Rat


CHLOROTHIAZIDE has been in use for several years as a diuretic drug. Its diuretic effect is usually ascribed to inhibition of sodium reabsorption in tubular cells1. In recent years Chlorothiazide has been reported to decrease urine volume in diabetes insipidus2. The autidiurietc effect is accompanied, however, by saluresis, that is, increased sodium excretion3. To explain the paradoxical action of Chlorothiazide it has been suggested that the drug could also affect thirst, by decreasing plasma osmolarity through increased urinary sodium loss4,5. We have recently reported that Chlorothiazide reduced water intake in bilaterally nephrectomized rats, thus demonstrating an extra-renal effect6. Osmotic receptors related to thirst regulation have been postulated to be located in the hypothalamus7,8. Stein and Seifter have recently reported chemical excitation of thirst by deposition of acetyl-oholine crystals through a cannula into a certain area in the hypothalamus9. Applying their technique, we have deposited Chlorothiazide crystals in the same area of the hypothalamus of rats, weighing 350–400 g, using the co-ordinates of Stein and Seifter9. In control animals either calcium carbonate or talc was deposited in the same location. Food and water were given freely and daily consumption was recorded. Water intake was found decreased in rats with hypothalamic Chlorothiazide deposit compared with the control animals (Fig. 1). No difference in food consumption was noted between the two groups and the difference in water intake persisted also after withdrawal of the food. That Chlorothiazide was not absorbed to any appreciable extent into the circulation was suggested by the lower urinary volume in the Chlorothiazide rats relative to the control animals (20–26 per cent less). Furthermore, the potassium/sodium ratio in the urine was the same in the Chlorothiazide and the control groups.

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GUTMAN, J., CHAIMOVITZ, M. Effect of Chlorothiazide on Water Consumption in the Rat. Nature 209, 410–411 (1966).

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