Acute influence of sodium valproate on sodium and chloride urinary excretion in rats

3 PharmaEast GmbH, Berlin, Germany There is increasing evidence indicating that certain drugs evoke adverse drug effects that depend on the gender of patients. Elucidation of gender-effect of various drugs by means of preclinical trials is an important field of pharmacology. The chloriuretic and natriuretic effect of valproates (VPA) had not been investigated earlier, so the aim of the present study was to define peculiarities of 24-h urinary sodium (Na) and chloride (Cl) excretion in young adult Wistar rats of both genders and to evaluate the influence of sodium valproate (VPA). We measured 24h urinary Na, Cl, creatinine and pH levels. Twenty-eight control intact Wistar rats (14 males and 14 females) and 26 Wistar rats (13 males and 13 females) were investigated after a single intragastric administration of 300 mg/kg VPA. In control intact Wistar rats, 24-h diuresis per 100 g of body weight, 24-h urinary Na excretion per 100 g of body weight and Na/Cl ratio in female rats were found significantly higher than in male rats. After a single administration of VPA, total 24-h diuresis and 24-h diuresis per 100 g of body weight were significantly higher in VPA rats of both genders. 24-h urine Na levels, 24-h urine Na excretion, 24-h urinary Na excretion per 100 g of body weight and the Na/creatinine ratio were significantly higher in VPA-male and VPA-female rats than in gender-matched controls. The 24-h urinary Cl excretion, 24-h urinary Cl excretion per 100 g of body weight and the Cl/creatinine ratio were found significantly higher in VPAmale than in VPA-female rats. These data show that VPA, alongside the diuretic effect, enhances Na and Cl excretion with urine. 24-h natriuretic and chloriduretic response to VPA in male rats was significantly higher than in female rats. The mechanism of such genderrelated effect is not clear.