scholarly journals High-Salt Loading Downregulates Nrf2 Expression in a Sodium-Dependent Manner in Renal Collecting Duct Cells

2020 ◽  
Vol 10 ◽  
Author(s):  
Mi Liu ◽  
Mokan Deng ◽  
Qimei Luo ◽  
Xianrui Dou ◽  
Zhanjun Jia
2001 ◽  
Vol 536 (3) ◽  
pp. 769-783 ◽  
Author(s):  
J. A. Sayer ◽  
G. S. Stewart ◽  
S. H. Boese ◽  
M. A. Gray ◽  
S. H. S. Pearce ◽  
...  

2021 ◽  
Author(s):  
Hideki Oe ◽  
Hatsumi Yoshiki ◽  
Xinmin Zha ◽  
Hisato Kobayashi ◽  
Yoshitaka Aoki ◽  
...  

Abstract Anticholinergics, therapeutic agents for overactive bladder, are clinically suggested to reduce urine output. We investigated whether this effect is due to bladder or kidney urine reabsorption. Various solutions were injected into the bladder of urethane-anesthetized SD rats. The absorption rate for 2 hr was examined following the intravenous administration of the anticholinergics imidafenacin (IM), atropine(AT), and tolterodine(TO). The bilateral ureter was then canulated and saline was administered to obtain a diuretic state. Anticholinergics or 1-deamino-[8-D-arginine]-vasopressin (dDAVP) were intravenously administered. After the IM and dDAVP administrations, the rat kidneys were immunostained with AQP2 antibody, and intracellular cAMP was measured. The absorption rate was ~10% of the saline injected into the bladder and constant even when anticholinergics were administered. The renal urine among peaked 2 hr after the saline administration. Each of the anticholinergics significantly suppressed the urine production in a dose-dependent manner, as did dDAVP. IM and dDAVP increased the intracellular cAMP levels and caused the AQP2 molecule to localize to the collecting duct cells' luminal side. The urinary reabsorption mechanism through the bladder epithelium was not activated by anticholinergic administration. Thus, anticholinergics suppress urine production via an increase in urine reabsorption in the kidneys' collecting duct cells via AQP2.


2019 ◽  
Vol 21 (1) ◽  
pp. 183
Author(s):  
Annarita Di Mise ◽  
Maria Venneri ◽  
Marianna Ranieri ◽  
Mariangela Centrone ◽  
Lorenzo Pellegrini ◽  
...  

Vasopressin V2 receptor (V2R) antagonists (vaptans) are a new generation of diuretics. Compared with classical diuretics, vaptans promote the excretion of retained body water in disorders in which plasma vasopressin concentrations are inappropriately high for any given plasma osmolality. Under these conditions, an aquaretic drug would be preferable over a conventional diuretic. The clinical efficacy of vaptans is in principle due to impaired vasopressin-regulated water reabsorption via the water channel aquaporin-2 (AQP2). Here, the effect of lixivaptan—a novel selective V2R antagonist—on the vasopressin-cAMP/PKA signaling cascade was investigated in mouse renal collecting duct cells expressing AQP2 (MCD4) and the human V2R. Compared to tolvaptan—a selective V2R antagonist indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia—lixivaptan has been predicted to be less likely to cause liver injury. In MCD4 cells, clinically relevant concentrations of lixivaptan (100 nM for 1 h) prevented dDAVP-induced increase of cytosolic cAMP levels and AQP2 phosphorylation at ser-256. Consistent with this finding, real-time fluorescence kinetic measurements demonstrated that lixivaptan prevented dDAVP-induced increase in osmotic water permeability. These data represent the first detailed demonstration of the central role of AQP2 blockade in the aquaretic effect of lixivaptan and suggest that lixivaptan has the potential to become a safe and effective therapy for the treatment of disorders characterized by high plasma vasopressin concentrations and water retention.


1986 ◽  
Vol 33 (2) ◽  
pp. 156-167 ◽  
Author(s):  
Will W. Minuth ◽  
Peter Gilbert ◽  
Günter Lauer ◽  
Klaus Aktories ◽  
Peter Gross

2009 ◽  
Vol 11 (4) ◽  
pp. 616-628 ◽  
Author(s):  
Christophe Pichon ◽  
Céline Héchard ◽  
Laurence du Merle ◽  
Christelle Chaudray ◽  
Isabelle Bonne ◽  
...  

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