We hypothesize that the inner medulla of the kangaroo rat Dipodomys merriami, a desert rodent that concentrates its urine to more than 6,000 mosmol/kgH(2)O water, provides unique examples of architectural features necessary for production of highly concentrated urine. To investigate this architecture, inner medullary nephron segments in the initial 3,000 μm below the outer medulla were assessed with digital reconstructions from physical tissue sections. Descending thin limbs of Henle (DTLs), ascending thin limbs of Henle (ATLs), and collecting ducts (CDs) were identified by immunofluorescence using antibodies that label segment-specific proteins associated with transepithelial water flux (aquaporin 1 and 2, AQP1 and AQP2) and chloride flux (the chloride channel ClC-K1); all tubules and vessels were labeled with wheat germ agglutinin. In the outer 3,000 μm of the inner medulla, AQP1-positive DTLs lie at the periphery of groups of CDs. ATLs lie inside and outside the groups of CDs. Immunohistochemistry and reconstructions of loops that form their bends in the outer 3,000 μm of the inner medulla show that, relative to loop length, the AQP1-positive segment of the kangaroo rat is significantly longer than that of the Munich-Wistar rat. The length of ClC-K1 expression in the prebend region at the terminal end of the descending side of the loop in kangaroo rat is about 50% shorter than that of the Munich-Wistar rat. Tubular fluid of the kangaroo rat DTL may approach osmotic equilibrium with interstitial fluid by water reabsorption along a relatively longer tubule length, compared with Munich-Wistar rat. A relatively shorter-length prebend segment may promote a steeper reabsorptive driving force at the loop bend. These structural features predict functionality that is potentially significant in the production of a high urine osmolality in the kangaroo rat.

Issaian T, Urity VB, Dantzler WH, Pannabecker TL. Architecture of vasa recta in the renal inner medulla of the desert rodent Dipodomys merriami: potential impact on the urine concentrating mechanism. Am J Physiol Regul Integr Comp Physiol 303: R748 -R756, 2012. First published August 22, 2012; doi:10.1152/ajpregu.00300.2012.-We hypothesize that the inner medulla of the kangaroo rat Dipodomys merriami, a desert rodent that concentrates its urine to over 6,000 mosmol/kg H2O, provides unique examples of architectural features necessary for production of highly concentrated urine. To investigate this architecture, inner medullary vascular segments in the outer inner medulla were assessed with immunofluorescence and digital reconstructions from tissue sections. Descending vasa recta (DVR) expressing the urea transporter UT-B and the water channel aquaporin 1 lie at the periphery of groups of collecting ducts (CDs) that coalesce in their descent through the inner medulla. Ascending vasa recta (AVR) lie inside and outside groups of CDs. DVR peel away from vascular bundles at a uniform rate as they descend the inner medulla, and feed into networks of AVR that are associated with organized clusters of CDs. These AVR form interstitial nodal spaces, with each space composed of a single CD, two AVR, and one or more ascending thin limbs or prebend segments, an architecture that may lead to solute compartmentation and fluid fluxes essential to the urine concentrating mechanism. Although we have identified several apparent differences, the tubulovascular architecture of the kangaroo rat inner medulla is remarkably similar to that of the Munich Wistar rat at the level of our analyses. More detailed studies are required for identifying interspecies functional differences. urea transport; UT-B; aquaporin; concentrating mechanism DURING THE PAST TWO DECADES the three-dimensional architecture of the rat renal medulla has become increasingly pertinent to development of advanced computational models of medullary function (5,12,13,15,37,38). Recent advances have been made in understanding the geometrical relationships of collecting ducts (CDs) and nephrons of the outer medulla and inner medulla (28, 40 -42). However, much remains to be learned about compartmentation arising from dynamic flow of fluid and solutes between these structures; compartmentation that is essential for understanding the role of the renal medulla in processes of urine concentration and sodium and water balance (6, 23). For each of these processes, blood flow through medullary vasculature is highly integrated with epithelial fluid and solute fluxes, and more complete understanding of vessel architecture and connectivity between descending vasa recta (DVR) and ascending vasa recta (AVR) will more clearly define this compartmentation. The classical studies of the kangaroo rat (33) and other desert species demonstrating tolerance to low water intake underscore the potential insights these species could offer in understanding vascular compartmentation (1, 2) and its ...

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We hypothesize that the inner medulla (IM) of Dipodomys merriami, a desert rodent that concentrates its urine to over 6000 mOsm/Kg water, provides extreme examples of architectural features most necessary for production of highly concentrated urine. Three‐dimensional architecture of vasculature and nephron segments in the IM was assessed with digital reconstructions from physical tissue sections. Descending and ascending vasa recta (DVR, AVR), descending thin limbs (DTLs), ascending thin limbs (ATLs), and collecting ducts (CDs) were identified by indirect immunofluorescence using antibodies that label segment‐specific proteins associated with solute and water transport and lectins (UT‐B, wheat germ lectin, AQP1, ClC‐K1, and AQP2, respectively). CD clusters form the central organizing motif in the IM. Transverse sections along the corticopapillary axis show nonuniform distribution of AQP‐1‐positive DTLs and uniform distribution of ATLs. Countercurrent exchange occurs only at the perimeter of CD clusters as DVR lie distant from CDs. Electron microscopy shows fenestrated AVR adhering to CDs. This architectural arrangement raises the possibility that fluid and solute reabsorbed from CDs diffuses preferentially into AVR. An additional factor increasing and defining axial compartmentation, and thereby restricting diffusive exchange, would be interstitial cell architecture. DK16294