American journal of physiology. Renal physiology
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Am. J. Physiol. Renal Physiol. · Sep 2008
Enhanced amiloride-sensitive superoxide production in renal medullary thick ascending limb of Dahl salt-sensitive rats.
The aims of the present study were to determine whether superoxide (O(2)(-)) production is enhanced in medullary thick ascending limb (mTAL) of Dahl salt-sensitive (SS) rats compared with a salt-resistant consomic control strain (SS.13(BN)) and to elucidate the cellular pathways responsible for augmented O(2)(-) production. Studies were carried out in 7- to 10-wk-old male SS and SS.13(BN) rats fed either a 0.4% NaCl diet or a 4.0% NaCl diet for 3 days before tissue harvest. Tissue strips containing mTAL were isolated from the left kidney, loaded with the O(2)(-)-sensitive fluorescent dye dihydroethidium, superfused with modified Hanks' solution, and imaged at x60 magnification on a heated microscope stage. ⋯ We conclude that mTAL from SS rats exhibit enhanced amiloride-sensitive O(2)(-) production. The amiloride-sensitive O(2)(-) response in mTAL is independent of active Na(+) transport and appears to be mediated by NAD(P)H oxidase. Amiloride-sensitive O(2)(-) production is likely to contribute to augmented outer medullary O(2)(-) production observed in SS rats during both normal and high NaCl diets.
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Am. J. Physiol. Renal Physiol. · Jul 2008
Sevoflurane protects against renal ischemia and reperfusion injury in mice via the transforming growth factor-beta1 pathway.
We previously demonstrated that several clinically utilized volatile anesthetics including sevoflurane protected against renal ischemia-reperfusion (IR) injury by reducing necrosis and inflammation in vivo. We also demonstrated that volatile anesthetics produced direct anti-necrotic and anti-inflammatory effects in cultured renal tubules via mechanisms involving the externalization of phosphatidylserine and subsequent release of transforming growth factor (TGF)-beta1. In this study, we tested the hypothesis that volatile anesthetic-mediated renal protection requires TGF-beta1 and SMAD3 signaling in vivo. ⋯ Sevoflurane caused nuclear translocation of SMAD3 and reduced the TNF-alpha-induced nuclear translocation of NF-kappaB in primary cultures of proximal tubules from TGF-beta1+/+ but not in TGF-beta1+/- mice. Finally, sevoflurane protected against necrosis induced with hydrogen peroxide in primary cultures of proximal tubules from TGF-beta1+/+ mice or SMAD3+/+ mice but not in proximal tubules from TGF-beta1+/- or SMAD3-/- mice. Therefore, we demonstrate in this study that sevoflurane-mediated renal protection in vivo requires the TGF-beta1-->SMAD3 signaling pathway.
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Am. J. Physiol. Renal Physiol. · Jun 2008
Quantitative analysis of functional reconstructions reveals lateral and axial zonation in the renal inner medulla.
Three-dimensional functional reconstructions of descending thin limbs (DTLs) and ascending thin limbs (ATLs) of loops of Henle, descending vasa recta (DVR), ascending vasa recta (AVR), and collecting ducts (CDs) permit quantitative definition of lateral and axial zones of probable functional significance in rat inner medulla (IM). CD clusters form the organizing motif for loops of Henle and vasa recta in the initial 3.0-3.5 mm of the IM. Using Euclidean distance mapping, we defined the lateral boundary of each cluster by pixels lying maximally distant from any CD. ⋯ Because approximately 3.0-3.5 mm below the IM base CD clusters cease to form the organizing motif, all DTLs lack aquaporin 1 (AQP1), and all vasa recta are fenestrated, we have designated the first 3.0-3.5 mm of the IM the "outer zone" (OZ) and the final 1.5-2.0 mm the "inner zone" (IZ). We further subdivided these into OZ-1, OZ-2, IZ-1, and IZ-2 on the basis of the presence of completely AQP1-null DTLs only in the first 1 mm and on broad transverse loop bends only in the final 0.5 mm. These transverse segments expand surface area for probable NaCl efflux around loop bends from approximately 40% to approximately 140% of CD surface area in the final 100 microm of the papilla.
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Am. J. Physiol. Renal Physiol. · Jun 2008
Aquaporin-2 downregulation in kidney medulla of aging rats is posttranscriptional and is abolished by water deprivation.
Aging kidney is associated in humans and rodents with polyuria and reduced urine concentrating ability. In senescent female WAG/Rij rats, this defect is independent of arginine-vasopressin (AVP)/V(2) receptor/cAMP pathway. It has been attributed to underexpression and mistargeting of aquaporin-2 (AQP2) water channel in the inner medullary collecting duct (IMCD). ⋯ In the outer medulla, preservation of AQP2 protein expression was achieved through increased AQP2 mRNA level in senescent rats. In the IMCD, no change in AQP2 mRNA was detected with aging but AQP2 protein expression was markedly lower in 30-mo-old animals. In conclusion, there is a posttranscriptional downregulation of AQP2 with aging, which is abolished by WD.
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Am. J. Physiol. Renal Physiol. · Jun 2008
Epithelial Na+ channel activation and processing in mice lacking SGK1.
Amiloride-sensitive Na(+) channel activity was examined in the cortical collecting ducts of a mouse line (SGK1(-/-)) deficient in the serum- and glucocorticoid-dependent protein kinase SGK1. This activity was correlated with changes in renal Na handling and in the maturation of epithelial Na(+) channel (ENaC) protein. Neither SGK1(-/-) mice nor paired SGK1(+/+) animals expressed detectable channel activity, measured as amiloride-sensitive whole-cell current (I(Na)), under control conditions with standard chow. ⋯ Despite the larger currents, the ratio of cleaved to full-length gamma-ENaC was lower in the knockout animals. The mice also expressed a smaller amount of Na(+)-Cl(-) cotransporter protein under Na-depleted conditions. These results indicated that SGK1 is essential for optimal processing of ENaC but is not required for activation of the channel by aldosterone.