TL;DR: The findings suggest that the mechanisms of water transport in the descending thin limbs of short loop nephrons should be reevaluated and the roles of aquaporin-1 and UT-A2 in the countercurrent multiplier and water conversation may need to be readdressed.
Abstract: In mammalian kidneys, aquaporin-1 is responsible for water reabsorption along the proximal tubule and is also thought to be involved in the concentration of urine that occurs in the medulla. It has been suggested, however, that aquaporin-1 is not expressed in the last part of the descending thin limbs of short loop nephrons in rats and mice, and its expression in this region in humans has not been studied. We examined the expression of aquaporin-1 and the urea transporter UT-A2 in serial sections of mouse nephrons in the inner stripe of the outer medulla using immunohistochemistry. In contrast to previous observations, we demonstrate a complete absence of aquaporin-1 along the entire length of descending thin limbs of 90% of short loop nephrons. Conversely, as expected, we identified aquaporin-1 in proximal tubules, descending thin limbs of long loop nephrons, and medullary descending vasa recta. We also observed this abrupt transition from aquaporin-1-positive proximal tubules to aquaporin-1-negative descending thin limbs of short loop nephrons in sections of human and rat kidneys. UT-A2 was restricted to the last 28% to 44% of the descending thin limbs of all short loop nephrons. Because the majority of nephrons are of the short loop variety, our findings suggest that the mechanisms of water transport in the descending thin limbs of short loop nephrons should be reevaluated. Likewise, the roles of aquaporin-1 and UT-A2 in the countercurrent multiplier and water conversation may need to be readdressed.
TL;DR: Investigation of the effect of increased extracellular tonicity/osmolarity on vasopressin-inducible aquaporin-2 (AQP2) expression in immortalized mouse collecting duct principal cells finds that on the long-term, vasopressingin (AVP) and hypertonicity increased AQP2 expression in a synergistic manner.
Abstract: The driving force for renal water reabsorption is provided by the osmolarity gradient between the interstitium and the tubular lumen, which is subject to rapid physiologic variations as a consequence of water intake fluctuations. The effect of increased extracellular tonicity/osmolarity on vasopressin-inducible aquaporin-2 (AQP2) expression in immortalized mouse collecting duct principal cells (mpkCCD(cl4)) is investigated in this report. Increasing the osmolarity of the medium either by the addition of NaCl, sucrose, or urea first decreased AQP2 expression after 3 h. AQP2 expression then increased in cells exposed to NaCl- or sucrose-supplemented hypertonic medium after longer periods of time (24 h), while urea-supplemented hyperosmotic medium had no effect. Altered AQP2 expression induced by both short-term (3 h) and long-term (24 h) exposure of cells to hypertonicity arose from changes in AQP2 gene transcription because hypertonicity did not modify AQP2 mRNA stability nor AQP2 protein turnover. On the long-term, vasopressin (AVP) and hypertonicity increased AQP2 expression in a synergistic manner. Hypertonicity altered neither the dose-responsiveness of AVP-induced AQP2 expression nor cAMP-protein kinase (PKA) activity, while PKA inhibition did not reduce the extent of the hypertonicity-induced increase of AQP2 expression. These results indicate that in collecting duct principal cells: (1) a short-term increase of extracellular osmolarity decreases AQP2 expression through inhibition of AQP2 gene transcription; (2) a long-term increase of extracellular tonicity, but not osmolarity, enhances AQP2 expression via stimulation of AQP2 gene transcription; and (3) long-term hypertonicity and PKA increases AQP2 expression through synergistic but independent mechanisms.
TL;DR: Although the rates of physiological processes showed marked diversity, proximal fractional reabsorption of salt and water was appropriate for the rate of filtration in individual nephrons and, thus, is evidence of the adaptive compensations which constitute the phenomena of chronic renal disease.
TL;DR: It is proposed that the deficient urine concentration ability and the inhibited potassium secretion are caused by the ischemic damage to the renal medulla, which will lead to interstitial and intracellular edema and eventually cell necrosis with subsequent formation of obstructions in the loops of Henle.
Abstract: Acute renal failure was induced in rats by clamping the renal artery for 45 min. After reestablishing renal blood flow, tubular heterogeneity was observed, with (1) seemingly normal tubules, (2) dilated tubules and (3) collapsed tubules. Micropuncture techniques were used to examine the hydrostatic pressures in the different nephrons and superficial vessels, and also to determine single nephron glomerular filtration rate. The dilated tubules showed minimal filtration, due to an elevated intratubular pressure probably caused by obstructions; in these nephrons filtration could be induced by lowering the intratubular pressure. In the “normal” nephrons there was some filtration, as the proximal tubular pressure was only moderately increased. No filtration took place in the collapsed type, probably as a result of glomerular ischemia and consequently decreased glomerular capillary pressure. The kidneys also exhibited isosthenuric polyuria with a reduced potassium secretion. It is suggested that a medullary isch...
TL;DR: Three-dimensional analysis of the vascular bundle of the mouse kidney strongly suggest a lateral osmolarity heterogeneity across the inner stripe of the outer medulla, which might work as a driving force for water and solute transport.
Abstract: The vascular bundle (VB) is a complex structure that resides in the inner stripe of the outer medulla. At present, the tubulovascular spatial organization of the VB, which is crucial for the formation of the osmolarity gradient and for solute transport, is still under debate. In this study, we used computer-assisted digital tracing combined with aquaporin-1 immunohistochemistry to reconstruct all tubules and vessels in the VB of the mouse kidney. We found, first, that the descending and ascending vasa recta travelled exclusively through the VB. The ascending vasa recta received no tributaries (no branches) along their entire path in the medulla and were not connected with the capillary plexus in the interbundle region. Second, a specific group of the descending vasa recta were closely accompanied by the longest ascending vasa recta, which connected only to the capillary plexus at the tip of the papilla. Third, the descending thin limbs of all short-looped nephrons travelled exclusively through the outer part of the VB. The loops of these nephrons (both descending and ascending parts) were distributed in a regular pattern based on their length. Finally, the thick ascending limbs of all long-looped nephrons were located at the margin of the VB (except a few within the VB), which formed a layer separating the VB from the interbundle region. In conclusion, our three-dimensional analysis of the VB strongly suggest a lateral osmolarity heterogeneity across the inner stripe of the outer medulla, which might work as a driving force for water and solute transport.