Role of UTB Urea Transporters in the Urine Concentrating Mechanism of the Rat Kidney |
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Authors: | Anita T Layton |
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Institution: | (1) Department of Mathematics, Duke University, Box 90320, Durham, NC 27708-0320, USA |
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Abstract: | A mathematical model of the renal medulla of the rat kidney was used to investigate urine concentrating mechanism function
in animals lacking the UTB urea transporter. The UTB transporter is believed to mediate countercurrent urea exchange between
descending vasa recta (DVR) and ascending vasa recta (AVR) by facilitating urea transport across DVR endothelia. The model
represents the outer medulla (OM) and inner medulla (IM), with the actions of the cortex incorporated via boundary conditions.
Blood flow in the model vasculature is divided into plasma and red blood cell compartments. In the base-case model configuration
tubular dimensions and transport parameters are based on, or estimated from, experimental measurements or immunohistochemical
evidence in wild-type rats. The base-case model configuration generated an osmolality gradient along the cortico-medullary
axis that is consistent with measurements from rats in a moderately antidiuretic state. When expression of UTB was eliminated
in the model, model results indicated that, relative to wild-type, the OM cortico-medullary osmolality gradient and the net
urea flow through the OM were little affected by absence of UTB transporter. However, because urea transfer from AVR to DVR
was much reduced, urea trapping by countercurrent exchange was significantly compromised. Consequently, urine urea concentration
and osmolality were decreased by 12% and 8.9% from base case, respectively, with most of the reduction attributable to the
impaired IM concentrating mechanism. These results indicate that the in vivo urine concentrating defect in knockout mouse,
reported by Yang et al. (J Biol Chem 277(12), 10633–10637, 2002), is not attributable to an OM concentrating mechanism defect,
but that reduced urea trapping by long vasa recta plays a significant role in compromising the concentrating mechanism of
the IM. Moreover, model results are in general agreement with the explanation of knockout renal function proposed by Yang
et al. |
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Keywords: | Renal medulla Urine concentrating mechanism Countercurrent system NaCl transport Urea transport Mathematical model |
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