Sodium dichloroacetate pharmacological effect as related to Na-K-2Cl cotransporter inhibition in rats

Abstract

The study objective was to investigate a possible sodium dichloroacetate (DCA) pharmacological mechanism causing an increase in diuresis in rats. The aim was to define characteristics of 24-hour urinary Naþ,Kþ, Cl , Ca 2þ, and Mg 2þ excretion in Wistar male rats and to evaluate effect of a single-dose DCA and repeated DCA dosage on diuresis. Six control and 6 DCAtreated male rats aged 5 to weeks after a single DCA dose and repeated dosage were tested. The single DCA dose treatment caused a significantly higher 24-hour diuresis when compared to control (P < .05), and it was related to increased Cl , Naþ, and Kþ urine excretion and a significant increase in Ca2þ and Mg2þ excretion (P < .05); after the repeated 4-week DCA dosage, the diuresis was not increased, but the excretion of the Naþ, Cl , Ca 2þ, and Mg 2þ ions was significantly higher. Kidney immunohistochemistry has revealed that DCA continuous treatment results in an increase in the size of Henle loop thick ascending limb epithelial cells (P < .001). The study results show a significantly reduced RNA expression of Na-K-2Cl co-transporter (NKCC1) in thymus of 4-week DCA-treated rats (P < .03). The study data have indicated a possible mechanism of such pharmacological effect to be NKCC inhibition.