Possible role of AQP3 in the concentration of non‐urea solutes in urine

Abstract

AQP3 is located in the cortical and medullary collecting duct (CD). Mice with AQP3 deletion (KO) exhibit a severe urinary concentrating defect, but are able, after 36 h dehydration, to concentrate urine to about 1/3 of the osmolality seen in wild-type (WT). In order to explore their concentrating defect further, we studied the influence of an acute urea load (UL = 300 μl of 1M urea, i.p.) in conscious KO and WT mice. Urine was collected every 2 h from 2 h before (Basal = B) to 8 h after the UL. During B, urine flow rate (V) was 3-fold higher and urine osmolality (Uosm) 3-fold lower in KO than in WT. Both genotypes excreted the UL in about 4 h with the same time-course. In the last 4 h, in WT mice, V fell below B values and Uosm, urea concentration (Uurea) and non-urea solute (NUS) concentration (U-NUS) rose above B values, in agreement with the well-known ability of urea to improve the capacity of the kidney to concentrate urine. Interestingly, after the UL, KO mice raised their Uosm and Uurea progressively to a dramatic extent so that these variables became almost equal to those in WT mice at 8 h. However, U-NUS did not change at all. V fell in the last 4 h to reach only 1/4 of B values. Thus, the excretion of NUS was significantly reduced, but not that of urea. These observations show that the lack of AQP3 improves the ability of the kidney to concentrate urea but impairs its ability to concentrate NUS. Because AQP3 is not only permeable to water but also to urea, it is conceivable that, in normal mice, some AQP3-mediated urea reabsorption in the CD may osmotically drive additional water and thus contribute to concentrate other solutes in the urine.