Effect of chlorothiazide on electrolyte excretion in intact and adrenalectomized rats

¹ Laboratory of Kidney and Electrolyte Metabolism, National Heart Institute, National Institutes of Health, Bethesda, Maryland

The acute effects of the oral administration of chlorothiazide on electrolyte and water excretion were studied in adrenalectomized and intact male Sprague-Dawley rats. After the administration of a sodium chloride and sodium bicarbonate load, urine for analysis was collected anaerobically for two consecutive 4-hr periods. Half of the intact and adrenalectomized animals received chlorothiazide, 200 mg/kg; the others served as controls. The diminished ability of adrenalectomized rats to excrete ammonia and sodium chloride was confirmed. In both the intact and adrenalectomized animals receiving chlorothiazide there was a significant and equivalent increase in urine pH, sodium, chloride, bicarbonate, total solute, and water excretion during the first 4 hr after administration of the drug when compared to the untreated controls. During the second 4 hr, there was no apparent response to chlorothiazide in either group. It is concluded that the diuretic effect of chlorothiazide is not a consequence of mineralocorticoid antagonism as has recently been proposed.