The Effects of Chlorothiazide on Sodium, Calcium, and Magnesium Transport in the Nephron of the Thyroparathyroidectomized Hamster
The chronic administration of thiazide diuretics results in a marked reduction in urinary calcium excretion which has proved to be of major benefit to patients with recurrent renal calculi1. The acute administration of thiazide diuretics results in a smaller increase in urinary calcium than sodium excretion1, 2. A number of renal and extrarenal factors have been implicated in explaining the chronic hypocalciuric action. First, thiazide diuretics have been shown in micropuncture studies to cause an increased sodium delivery from the distal tubule with little change in calcium delivery, implying a selective inhibition of distal sodium transport and possibly an increase in distal calcium reabsorption3. Second, thiazides may lead to depletion of extracellular fluid volume resulting in an enhanced proximal reabsorption of sodium and calcium and a reduced delivery of both ions to the more distal nephron segments where thiazides primarily inhibit sodium reabsorption. Urinary sodium excretion then returns to a control value while calcium excretion falls below control levels. Third, hypocalciuria may not readily develop in hypoparathyroid patients following thiazide administration and a role for parathyroid hormone has been implicated in the hypocalciuric action of thiazides4, 5. A number of recent reports are relevant to these observations. Most important, Costanza and Windhager have demonstrated a direct effect of chlorothiazide on calcium transport in micropuncture studies of the distal tubule of the rat6. Thus, thiazides would appear to decrease sodium transport and increase calcium reabsorption in the distal convoluted tubule. Further evidence indicates that the acute dissociation of sodium from calcium reabsorption with chlorothiazide is independent of circulating parathyroid hormone implying different cellular mechanisms of these two agents on distal tubular function7.
KeywordsThiazide Diuretic Distal Tubule Urinary Calcium Excretion Distal Convoluted Tubule Urinary Sodium Excretion
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