EFFECT OF N-(3,5-DICHLOROPHENYL)-2-HYDROXYSUCCINIMIDE ON RENAL-FUNCTION AND HEMODYNAMICS IN THE ANESTHETIZED RAT

The experimental agricultural fungicide N-(3,5-dichlorophenyl)succinim ide (NDPS) is a nephrotoxicant in the Fischer 344 rat. NDPS induces ne phrotoxicity via metabolic bioactivation to one or more metabolites. B oth N-(3,5-dichlorophenyl)-2-hydroxysuccinimide (NDHS) and N-(3,5-dich lorophenyl)-2-hydroxysuccinamic acid (NDHSA), oxidative metabolites of NDPS, are more potent nephrotoxicants than the parent compound. Preli minary studies in our laboratory indicate that altered renal hemodynam ics may contribute to the mechanism of NDPS-induced nephrotoxicity. Ho wever, it is not known if NDPS affects renal hemodynamics prior to or after altering tubular function. In this study, male Fischer 344 rats (275-300 g) were anesthetized with urethane (1.5 g/kg, i.p.) and prepa red for renal function experiments. Renal blood flow (RBF), glomerular filtration rate (GFR), urine flow rate (V) and fraction of GFR excret ed as urine (V/GFR) were determined during eight 30 min intervals foll owing NDHS (0.2 or 0.4 mmol/kg, i.p.) or vehicle (sesame oil, 2.5 ml/k g, i.p.) treatment. NDHS (0.2 or 0.4 mmol/kg) decreased GFR while urin e flow rate and V/GFR were increased compared to vehicle-treated contr ols. These alterations in renal function were evident by 2 h post NDHS (0.4 mmol/kg) and by 3 h post-NDHS (0.2 mmol/kg) treatment. RBF of ra ts receiving NDHS (0.2 or 0.4 mmol/kg) tended to decrease post-NDHS tr eatment; however, this decrease was not significant. Results of this s tudy indicate that NDHS (0.2 or 0.4 mmol/kg) initially alters renal fu nction by reducing the tubular reabsorption of glomerular filtrate pri or to a reduction of GFR and RBF.