American journal of physiology. Renal physiology
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Am. J. Physiol. Renal Physiol. · Oct 2010
PTH increases FGF23 gene expression and mediates the high-FGF23 levels of experimental kidney failure: a bone parathyroid feedback loop.
Parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) target the kidney to cause a phosphaturia. FGF23 also acts on the parathyroid to decrease PTH expression, but in chronic kidney disease (CKD) there are high-serum PTH and FGF23 levels and resistance of the parathyroid to FGF23. We now report that PTH acts on bone to increase FGF23 expression and characterize the signal transduction pathway whereby PTH increases FGF23 expression. ⋯ Therefore, PTH increases FGF23 expression which involves the PKA and Wnt pathways. The effect of PTH on FGF23 completes a bone-parathyroid endocrine feedback loop. Importantly, secondary hyperparathyroidism is essential for the high-FGF23 levels in early CKD.
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Am. J. Physiol. Renal Physiol. · Sep 2010
Nitric oxide and superoxide transport in a cross section of the rat outer medulla. II. Reciprocal interactions and tubulovascular cross talk.
In a companion study (Edwards A and Layton AT. Am J Physiol Renal Physiol. doi:10.1152/ajprenal.00680.2009), we developed a mathematical model of nitric oxide (NO), superoxide (O(2)(-)), and total peroxynitrite (ONOO) transport in mid-outer stripe and mid-inner stripe cross sections of the rat outer medulla (OM). We examined how the three-dimensional architecture of the rat OM, together with low medullary oxygen tension (Po(2)), affects the distribution of NO, O(2)(-), and ONOO in the rat OM. ⋯ The lower the P(NO)(RBC), the lower the amount of NO that is scavenged by hemoglobin species, and the higher the extra-erythrocyte NO concentrations. In addition, our results indicate that basal endothelial NO production acts to significantly limit NaCl reabsorption across medullary thick ascending limbs and to sustain medullary perfusion, whereas basal epithelial NO production has a smaller impact on NaCl transport and a negligible effect on vascular tone. Our model also predicts that O(2)(-) consumption by NO significantly reduces medullary O(2)(-) concentrations, but that O(2)(-) , when present at subnanomolar concentrations, has a small impact on medullary NO bioavailability.
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Am. J. Physiol. Renal Physiol. · Sep 2010
Nitric oxide and superoxide transport in a cross section of the rat outer medulla. I. Effects of low medullary oxygen tension.
To examine the impact of the complex radial organization of the rat outer medulla (OM) on the distribution of nitric oxide (NO), superoxide (O(2)(-)) and total peroxynitrite (ONOO), we developed a mathematical model that simulates the transport of those species in a cross section of the rat OM. To simulate the preferential interactions among tubules and vessels that arise from their relative radial positions in the OM, we adopted the region-based approach developed by Layton and Layton (Am J Physiol Renal Physiol 289: F1346-F1366, 2005). In that approach, the structural organization of the OM is represented by means of four concentric regions centered on a vascular bundle. ⋯ Model results suggest that the large gradients in Po(2) from the core of the vascular bundle toward its periphery, which stem from the segregation of O(2)-supplying descending vasa recta (DVR) within the vascular bundles, in turn generate steep radial NO and O(2)(-) concentration gradients, since the synthesis of both solutes is O(2) dependent. Without the rate-limiting effects of O(2), NO concentration would be lowest in the vascular bundle core, that is, the region with the highest density of RBCs, which act as a sink for NO. Our results also suggest that, under basal conditions, the difference in NO concentrations between DVR that reach into the inner medulla and those that turn within the OM should lead to differences in vasodilation and preferentially increase blood flow to the inner medulla.
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Am. J. Physiol. Renal Physiol. · Sep 2010
Interaction between vasopressin and angiotensin II in vivo and in vitro: effect on aquaporins and urine concentration.
The study was undertaken to examine the potential cross talk between vasopressin and angiotensin II (ANG II) intracellular signaling pathways. We investigated in vivo and in vitro whether vasopressin-induced water reabsorption could be attenuated by ANG II AT1 receptor blockade (losartan). On a low-sodium diet (0.5 meq/day) dDAVP-treated animals with or without losartan exhibited comparable renal function [creatinine clearance 1.2 +/- 0.1 in dDAVP+losartan (LSDL) vs. 1.1 +/- 0.1 ml.100 g(-1).day(-1) in dDAVP alone (LSD), P > 0.05] and renal blood flow (6.3 +/- 0.5 in LSDL vs. 6.8 +/- 0.5 ml/min in LSD, P > 0.05). ⋯ In vitro studies showed that ANG II or dDAVP treatment was associated with increased AQP2 expression and cAMP levels, which were potentiated by cotreatment with ANG II and dDAVP and were inhibited by AT1 blockade. In conclusion, ANG II AT1 receptor blockade in dDAVP-treated rats on a low-salt diet was associated with decreased urine concentration and decreased inner medullary AQP2, p-AQP2, and AQP3 expression, suggesting that AT1 receptor activation plays a significant role in regulating aquaporin expression and modulating urine concentration in vivo. Studies in collecting duct cells were confirmatory.
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Am. J. Physiol. Renal Physiol. · Jul 2010
Comparative StudyBioimpedance spectroscopy for the estimation of body fluid volumes in mice.
Conventional indicator dilution techniques for measuring body fluid volume are laborious, expensive, and highly invasive. Bioimpedance spectroscopy (BIS) may be a useful alternative due to being rapid, minimally invasive, and allowing repeated measurements. BIS has not been reported in mice; hence we examined how well BIS estimates body fluid volume in mice. ⋯ Further evaluation of the sensitivity of the BIS system was determined by its ability to detect volume changes after saline infusion; saline provided the predicted changes in compartmental fluid volumes. In summary, BIS is a noninvasive and accurate method for the estimation of body composition in mice. The ability to perform serial measurements will be a useful tool for future studies.