Background and Aims Urea plays important roles in urinary concentrating mechanisms in the kidney by contributing greatly in generation of hyperosmolar medulla, due to presence of urea transporters which mediate facilitated transport of urea. Urea transporter knock-out mice were reported to have increased daily urine volume. In this study, we investigated the possible diuretic effect of a urea analog and urea transporter inhibitor, dimethythiourea (DMTU), in rats.
Methods Female Wistar rats were divided into two groups, group 1 (Control, n=7) rats were injected with saline (ip), whereas group 2 (DMTU, n=7) rats were injected with 500 mg/kg DMTU (ip) and an additional dose of 125 mg/kg DMTU 8 h after.
Results DMTU administration induced a ~3 times increase in daily urine volume (p<0.001) and decreased urine osmolality to ~%35 of controls (p<0.0001). DMTU also increased free water clearance (p<0.0001) without a significant change in osmolar clearance. DMTU treatment caused an increase in urea clearance (p<0.05) and fractional excretion of urea (p<0.05) with a decrease in serum urea concentration (p<0.001). DMTU had no effect on creatinine clearance or serum electrolytes, creatinine levels and osmolality.
Conclusions We report for the first time that DMTU has a prominent diuretic effect with increased urea excretion, which may be explained by the inhibitory effect of the drug on urea transporters. Our findings suggest that DMTU may be used as a diuretic agent and also could be used as a lead compound for development of a novel group of diuretics.