American journal of physiology. Renal physiology
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Am. J. Physiol. Renal Physiol. · Oct 2006
Glucocorticoid impairs growth of kidney outer medulla and accelerates loop of Henle differentiation and urinary concentrating capacity in rat kidney development.
In the rat, urinary concentrating ability develops progressively during the third postnatal (P) week and nearly reaches adult level at weaning (P21) governed by a rise in circulating glucocorticoid. Elevated extracellular osmolality can lead to growth arrest of epithelial cells. We tested the hypothesis that supranormal exposure of rat pups to glucocorticoid before the endogenous surge enhances urinary concentrating ability but inhibits renomedullary cell proliferation. ⋯ We conclude that a low level of circulating glucocorticoid is permissive for proliferation of Henle's loop and the outer medulla before weaning. A reduced papillary tonicity is a crucial factor for the reduced capacity to concentrate urine during postnatal kidney development. We speculate that supranormal exposure to glucocorticoid in the suckling period can alter kidney medullary structure and function permanently.
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Am. J. Physiol. Renal Physiol. · Sep 2006
Tissue oxygen and hemodynamics in renal medulla, cortex, and corticomedullary junction during hemorrhage-reperfusion.
Previous studies of intrarenal perfusion and tissue oxygenation have produced a wide range of results and have not matched tissue oxygen tension (tPo(2)) with concurrent changes in flow in three distinct regions. We thus used an anesthetized rat model of hemorrhage-reperfusion to address this question. Combined tpo(2)/laser-Doppler fiber-optic probes were simultaneously sited in cortical, corticomedullary (CMJ), and medullary regions of the left kidney. ⋯ The ratio of tpo(2) to microvascular blood flow increased significantly in all regions during resuscitation, suggesting decreased oxygen consumption. On total cessation of blood flow, the cortex and CMJ showed significant increases in the oxygen decay half-life, consistent with decreased consumption. To our knowledge, this is the first quantitative demonstration of a markedly heterogeneous intrarenal cardiorespiratory response to a hemodynamic insult, with effects most marked at the corticomedullary junction.
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Am. J. Physiol. Renal Physiol. · Aug 2006
ReviewCell biological aspects of the vasopressin type-2 receptor and aquaporin 2 water channel in nephrogenic diabetes insipidus.
In the renal collecting duct, water reabsorption is regulated by the antidiuretic hormone vasopressin (AVP). Binding of this hormone to the vasopressin V2 receptor (V2R) leads to insertion of aquaporin-2 (AQP2) water channels in the apical membrane, thereby allowing water reabsorption from the pro-urine to the interstitium. ⋯ This review describes the current knowledge of the cell biological causes of NDI and how these defects may explain the patients' phenotypes. Also, the increased understanding of these cellular defects in NDI has opened exciting initiatives in the development of novel therapies for NDI, which are extensively discussed in this review.
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Am. J. Physiol. Renal Physiol. · Aug 2006
Mouse model of inducible nephrogenic diabetes insipidus produced by floxed aquaporin-2 gene deletion.
Transgenic mouse models of defective urinary concentrating ability produced by deletion of various membrane transport or receptor proteins, including aquaporin-2 (AQP2), are associated with neonatal mortality from polyuria. Here, we report an inducible mouse model of AQP2 gene deletion with severe polyuria in adult mice. LoxP sequences were inserted into introns 1 and 2 in the mouse AQP2 gene by homologous recombination in embryonic stem cells. ⋯ Interestingly, AQP3 protein expression in the collecting duct was increased by about fivefold after AQP2 gene excision. Mild renal damage was seen after 6 wk of polyuria, with collecting duct dilatation, yet normal creatinine clearance and serum chemistries. These results establish the first adult model of nephrogenic diabetes insipidus (NDI) caused by AQP2 deficiency, with daily urine output comparable to body weight, although remarkable preservation of renal function compared with non-inducible NDI models.
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Am. J. Physiol. Renal Physiol. · Aug 2006
Urea and urine concentrating ability in mice lacking AQP1 and AQP3.
Aquaporin-1 (AQP1) and aquaporin-3 (AQP3) water channels expressed in the kidney play a critical role in the urine concentrating mechanism. Mice with AQP1 or AQP3 deletion have a urinary concentrating defect. To better characterize this defect, we studied the influence of an acute urea load (300 mumol ip) in conscious AQP1-null, AQP3-null, and wild-type mice. ⋯ These observations show that the lack of AQP3 does not interfere with the ability of the kidney to concentrate urea but impairs its ability to concentrate other solutes. This solute-selective response could result from the capacity of AQP3 to transport not only water but also urea. The results suggest a novel role for AQP3 in non-urea solute concentration in the urine.