Effect of chlorothiazide on electrolyte excretion in intact and adrenalectomized rats

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Abstract
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.