scholarly journals The Absence of Endothelial Sodium Channel α (αENaC) Reduces Renal Ischemia/Reperfusion Injury

2019 ◽  
Vol 20 (13) ◽  
pp. 3132 ◽  
Author(s):  
Antoine Tarjus ◽  
Cecilia González-Rivas ◽  
Isabel Amador-Martínez ◽  
Benjamin Bonnard ◽  
Rebeca López-Marure ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Sodium Channel ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Cell Stiffness ◽  
Mrna Levels ◽  
Lipocalin 2 ◽  
Tubular Injury ◽  
No Bioavailability

The epithelial sodium channel (ENaC) has a key role in modulating endothelial cell stiffness and this in turn regulates nitric oxide (NO) synthesis. The physiological relevance of endothelial ENaC in pathological conditions where reduced NO bioavailability plays an essential role remains largely unexplored. Renal ischemia/reperfusion (IR) injury is characterized by vasoconstriction and sustained decrease in renal perfusion that is partially explained by a reduction in NO bioavailability. Therefore, we aimed to explore if an endothelial ENaC deficiency has an impact on the severity of renal injury induced by IR. Male mice with a specific endothelial sodium channel α (αENaC) subunit gene inactivation in the endothelium (endo-αENaCKO) and control littermates were subjected to bilateral renal ischemia of 22 min and were studied after 24 h of reperfusion. In control littermates, renal ischemia induced an increase in plasma creatinine and urea, augmented the kidney injury molecule-1 (Kim-1) and neutrophil gelatinase associated lipocalin-2 (NGAL) mRNA levels, and produced severe tubular injury. The absence of endothelial αENaC expression prevented renal tubular injury and renal dysfunction. Moreover, endo-αENaCKO mice recovered faster from renal hypoxia after the ischemia episode as compared to littermates. In human endothelial cells, pharmacological ENaC inhibition promoted endothelial nitric oxide synthase (eNOS) coupling and activation. Altogether, these data suggest an important role for endothelial αENaC in kidney IR injury through improving eNOS activation and kidney perfusion, thus, preventing ischemic injury.

Adrenalectomy prevents renal ischemia-reperfusion injury

2009 ◽  
Vol 297 (4) ◽  
pp. F932-F942 ◽  
Author(s):  
Victoria Ramírez ◽  
Joyce Trujillo ◽  
Rafael Valdes ◽  
Norma Uribe ◽  
Cristino Cruz ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Renal Dysfunction ◽  
Renal Damage ◽  
Ischemia Reperfusion Injury ◽  
Therapeutic Option ◽  
Ischemia Reperfusion ◽  
Rho Kinase ◽  
Tubular Damage ◽  
Mrna Levels ◽  
Tubular Injury

Spironolactone treatment prevents renal damage induced by ischemia-reperfusion (I/R), suggesting that renoprotection conferred by spironolactone is mediated by mineralocorticoid receptor (MR) blockade. It is possible, however, that this effect is due to other mechanisms. Therefore, this study evaluated whether adrenalectomy prevented renal damage induced by I/R. Three groups of Wistar rats were studied: 1) a group subjected to a sham surgery, 2) a group subjected to bilateral I/R, and 3) a group of rats in which adrenal glands were removed 3 days before induction of I/R. As expected, I/R resulted in renal dysfunction and severe tubular injury that was associated with a significant increase in tubular damage markers. In contrast, there was no renal dysfunction or tubular injury in rats that were adrenalectomized before I/R. These effects were demonstrated by normalization of glomerular filtration rate, markers of oxidative stress, and tubular injury markers in adrenalectomized rats. The renoprotection observed was associated with the reestablishment of nitric oxide metabolites, increased endothelial nitric oxide synthase expression and its activating phosphorylation, as well as normalization of Rho-kinase expression and ETA mRNA levels. Our results show that aldosterone plays a central role in the pathogenesis of renal damage induced by I/R and that MR blockade may be a promising strategy that opens a new therapeutic option for preventing acute renal injury.

Expression of SSAT, a novel biomarker of tubular cell damage, increases in kidney ischemia-reperfusion injury

2003 ◽  
Vol 284 (5) ◽  
pp. F1046-F1055 ◽  
Author(s):  
Kamyar Zahedi ◽  
Zhaohui Wang ◽  
Sharon Barone ◽  
Anne E. Prada ◽  
Caitlin N. Kelly ◽  
...  
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Reperfusion Injury ◽  
Cell Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Atp Depletion ◽  
Tubular Cell ◽  
Mrna Levels ◽  
Tubular Injury

Ischemia-reperfusion injury (IRI) is the major cause of acute renal failure in native and allograft kidneys. Identifying the molecules and pathways involved in the pathophysiology of renal IRI will yield valuable new diagnostic and therapeutic information. To identify differentially regulated genes in renal IRI, RNA from rat kidneys subjected to an established renal IRI protocol (bilateral occlusion of renal pedicles for 30 min followed by reperfusion) and time-matched kidneys from sham-operated animals was subjected to suppression subtractive hybridization. The level of spermidine/spermine N 1-acetyltransferase (SSAT) mRNA, an essential enzyme for the catabolism of polyamines, increased in renal IRI. SSAT expression was found throughout normal kidney tubules, as detected by nephron segment RT-PCR. Northern blots demonstrated that the mRNA levels of SSAT are increased by greater than threefold in the renal cortex and by fivefold in the renal medulla at 12 h and returned to baseline at 48 h after ischemia. The increase in SSAT mRNA was paralleled by an increase in SSAT protein levels as determined by Western blot analysis. The concentration of putrescine in the kidney increased by ∼4- and ∼7.5-fold at 12 and 24 h of reperfusion, respectively, consistent with increased functional activity of SSAT. To assess the specificity of SSAT for tubular injury, a model of acute renal failure from Na+depletion (without tubular injury) was studied; SSAT mRNA levels remained unchanged in rats subjected to Na+ depletion. To distinguish SSAT increases from the effects of tubular injury vs. uremic toxins, SSAT was increased in cis-platinum-treated animals before the onset of renal failure. The expression of SSAT mRNA and protein increased by ∼3.5- and >10-fold, respectively, in renal tubule epithelial cells subjected to ATP depletion and metabolic poisoning (an in vitro model of kidney IRI). Our results suggest that SSAT is likely a new marker of tubular cell injury that distinguishes acute prerenal from intrarenal failure.

Protective Effect of Nitric Oxide Pathway in L-Citrulline Renal Ischemia-Reperfusion Injury in Rats

2013 ◽  
Vol 634-638 ◽  
pp. 1357-1361
Author(s):  
Xin Ling ◽  
Xiao Bin Fu ◽  
Li Liu ◽  
Xia Tian ◽  
Ling Yan Sun ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Renal Cortex ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Protective Effects ◽  
Significant Protection ◽  
Renal Ischemia Reperfusion Injury ◽  
Reperfusion Period ◽  
Oxide Synthase

To observe the protective effects of L-citrulline on the renal ischemia-reperfusion (I/R) injury and elucidate the mechanisms involved. Forty-eight rats were randomized into eight groups. At the end of the reperfusion period, serum was collected and the kidneys were removed for histological and biochemical examinations. Our results showed that pretreatment with L-citrulline significantly ameliorated the renal injury caused by I/R. Moreover, L-citrulline increased the levels of NO. The I/R-induced decreases in total nitric oxide synthase (NOS) activity, inducible NOS activity and constitutive NOS activity in the renal cortex were significantly prevented. These results suggested that L-citrulline administration exhibited significant protection on renal I/R injury.

Intrarenal Administration of Molsidomine, a Molecule Releasing Nitric Oxide, Reduces Renal Ischemia-Reperfusion Injury in Rats

2004 ◽  
Vol 4 (10) ◽  
pp. 1605-1613 ◽  
Author(s):  
Ana Rodriguez-Pena ◽  
Francisco J. Garcia-Criado ◽  
Nelida Eleno ◽  
Miguel Arevalo ◽  
Jose M. Lopez-Novoa
Keyword(s):  
Nitric Oxide ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Renal Ischemia Reperfusion Injury

scholarly journals Inhibition of inducible nitric oxide synthase reduces renal ischemia/reperfusion injury

2002 ◽  
Vol 61 (3) ◽  
pp. 862-871 ◽  
Author(s):  
Prabal K. Chatterjee ◽  
Nimesh S.A. Patel ◽  
Espen O. Kvale ◽  
Salvatore Cuzzocrea ◽  
Paul A.J. Brown ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Reperfusion Injury ◽  
Inducible Nitric Oxide Synthase ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Renal Ischemia Reperfusion Injury ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Differential expression and localization of tubular injury markers NGAL and KIM-1 in a rat model of renal ischemia/reperfusion injury

2014 ◽  
Vol 31 (4) ◽  
pp. 246
Author(s):  
Pieter van der Pol ◽  
Dianne Vreeken ◽  
Danielle J. van Gijlswijk-Jansen ◽  
Nicole Schlagwein ◽  
Johan W. de Fijter ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Differential Expression ◽  
Rat Model ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Tubular Injury ◽  
Renal Ischemia Reperfusion Injury

The role of nitric oxide pathway in the renal ischemia–reperfusion injury in rats

2002 ◽  
Vol 10 (4) ◽  
pp. 277-284 ◽  
Author(s):  
Ernani Luı́s Rhoden ◽  
Cláudia Ramos Rhoden ◽  
Márcio Luı́s Lucas ◽  
Luiz Pereira-Lima ◽  
Cláudio Zettler ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Renal Ischemia Reperfusion Injury ◽  
Nitric Oxide Pathway

scholarly journals Deletion of the Gamma Subunit of ENaC in Endothelial Cells Does Not Protect against Renal Ischemia Reperfusion Injury

2021 ◽  
Vol 22 (20) ◽  
pp. 10914
Author(s):  
Stephanie M. Mutchler ◽  
Mahpara Hasan ◽  
Donald E. Kohan ◽  
Thomas R. Kleyman ◽  
Roderick J. Tan
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Renal Ischemia ◽  
Α Subunit ◽  
Γ Subunit ◽  
Renal Ischemia Reperfusion Injury

Acute kidney injury due to renal ischemia-reperfusion injury (IRI) may lead to chronic or end stage kidney disease. A greater understanding of the cellular mechanisms underlying IRI are required to develop therapeutic options aimed at limiting or reversing damage from IRI. Prior work has shown that deletion of the α subunit of the epithelial Na+ channel (ENaC) in endothelial cells protects from IRI by increasing the availability of nitric oxide. While canonical ENaCs consist of an α, β, and γ subunit, there is evidence of non-canonical ENaC expression in endothelial cells involving the α subunit. We therefore tested whether the deletion of the γ subunit of ENaC also protects mice from IRI to differentiate between these channel configurations. Mice with endothelial-specific deletion of the γ subunit and control littermates were subjected to unilateral renal artery occlusion followed by 48 h of reperfusion. No significant difference was noted in injury between the two groups as assessed by serum creatinine and blood urea nitrogen, levels of specific kidney injury markers, and histological examination. While deletion of the γ subunit did not alter infiltration of immune cells or cytokine message, it was associated with an increase in levels of total and phosphorylated endothelial nitric oxide synthase (eNOS) in the injured kidneys. Our studies demonstrate that even though deletion of the γ subunit of ENaC may allow for greater activation of eNOS, this is not sufficient to prevent IRI, suggesting the protective effects of α subunit deletion may be due, in part, to other mechanisms.

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