scholarly journals 5/6th Nephrectomy in Combination with High Salt Diet and Nitric Oxide Synthase Inhibition to Induce Chronic Kidney Disease in the Lewis Rat

10.3791/50398 ◽  
2013 ◽  
Author(s):  
Arianne van Koppen ◽  
Marianne C. Verhaar ◽  
Lennart G. Bongartz ◽  
Jaap A. Joles
Keyword(s):  
Nitric Oxide ◽  
Chronic Kidney Disease ◽  
Nitric Oxide Synthase ◽  
Kidney Disease ◽  
High Salt ◽  
Lewis Rat ◽  
High Salt Diet ◽  
Salt Diet ◽  
Oxide Synthase

High salt intake reduces endothelium-dependent dilation of mouse arterioles via superoxide anion generated from nitric oxide synthase

2007 ◽  
Vol 292 (4) ◽  
pp. R1550-R1556 ◽  
Author(s):  
Timothy R. Nurkiewicz ◽  
Matthew A. Boegehold
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Nitric Oxide Synthase ◽  
Superoxide Anion ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
High Salt Intake ◽  
Oxide Synthase ◽  
The Impact

In skeletal muscle arterioles of normotensive rats fed a high salt diet, the bioavailability of endothelium-derived nitric oxide (NO) is reduced by superoxide anion. Because the impact of dietary salt on resistance vessels in other species is largely unknown, we investigated endothelium-dependent dilation and oxidant activity in spinotrapezius muscle arterioles of C57BL/6J mice fed normal (0.45%, NS) or high salt (7%, HS) diets for 4 wk. Mean arterial pressure in HS mice was not different from that in NS mice, but the magnitude of arteriolar dilation in response to different levels of ACh was 42–57% smaller in HS mice than in NS mice. Inhibition of nitric oxide synthase (NOS) with NG monomethyl l-arginine (l-NMMA) significantly reduced resting diameters and reduced responses to ACh (by 45–63%) in NS mice but not in HS mice. Arteriolar wall oxidant activity, as assessed by tetranitroblue tetrazolium reduction or hydroethidine oxidation, was greater in HS mice than in NS mice. Exposure to the superoxide scavenger 2,2,6,6-tetramethylpiperidine- N-oxyl (TEMPO) + catalase reduced this oxidant activity to normal and restored normal arteriolar responsiveness to ACh in HS mice but had no effect in NS mice. l-NMMA also restored arteriolar oxidant activity to normal in HS mice. ACh further increased arteriolar oxidant activity in HS mice but not in NS mice, and this effect was prevented with l-NMMA. These data suggest that a high salt diet promotes increased generation of superoxide anion from NOS in the murine skeletal muscle microcirculation, thus impairing endothelium-dependent dilation through reduced NO bioavailability.

Triiodothyronine attenuates the progression of renal injury in a rat model of chronic kidney disease

2018 ◽  
Vol 96 (6) ◽  
pp. 603-610 ◽  
Author(s):  
Sahar M. El Agaty
Keyword(s):  
Nitric Oxide ◽  
Chronic Kidney Disease ◽  
Nitric Oxide Synthase ◽  
Kidney Disease ◽  
Renal Injury ◽  
Serum Levels ◽  
Female Rats ◽  
Renal Tubules ◽  
Oxide Synthase ◽  
Remnant Kidney

This study was designed to investigate whether and how triiodothyronine (T3) affects renal function in an experimental model of chronic kidney disease. Twenty-four female rats were divided into the following groups: sham-operated control group (n = 8), 5/6 nephrectomized group (Nx, n = 8), and 5/6 nephrectomized group treated with T3 for 2 weeks (T3-Nx, n = 8). T3 administration significantly decreased serum levels of urea, creatinine, tumour necrosis factorα, and interleukin-6 compared with serum levels in the Nx group. The levels of malondialdehyde, transforming growth factor β, fibronectin, and collagen IV, as well as the expression of inducible nitric oxide synthase, nuclear factor κB, poly(ADP-ribose) polymerase, caspase-3, and Bax were all significantly decreased, though not normalized, in the remnant kidney of rats in the T3-Nx group compared with Nx rats. Glutathione, heme oxygenase-1 levels, as well as endothelial nitric oxide synthase expression were increased in the remnant kidney of the T3-Nx group. Histological studies revealed focal necrosis of renal tubules associated with inflammatory cell infiltration and fibrosis in the Nx group. These changes were alleviated in T3-Nx rats. This study showed that T3 administration attenuated the clinical and histological signs of renal injury in 5/6 nephrectomized rats by mitigating renal oxidative stress, inflammation, apoptosis, and fibrosis.

scholarly journals Endothelial Nitric Oxide Synthase Gene Variation Associated With Chronic Kidney Disease After Liver Transplant

2010 ◽  
Vol 85 (9) ◽  
pp. 814-820 ◽  
Author(s):  
Kiran Bambha ◽  
W. Ray Kim ◽  
Charles B. Rosen ◽  
Rachel A. Pedersen ◽  
Cynthia Rys ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Chronic Kidney Disease ◽  
Nitric Oxide Synthase ◽  
Kidney Disease ◽  
Liver Transplant ◽  
Endothelial Nitric Oxide Synthase ◽  
Gene Variation ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Dietary Salt Modifies the Blood Pressure Response to Renin-Angiotensin Inhibition in Experimental Chronic Kidney Disease

2021 ◽  
Author(s):  
Dominique M Bovee ◽  
Estrellita Uijl ◽  
David Severs ◽  
Eloisa Rubio-Beltrán ◽  
Richard van Veghel ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
High Salt ◽  
Dietary Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Renin Angiotensin ◽  
Water Accumulation ◽  
Salt Sensitive Hypertension

Chronic kidney disease (CKD) contributes to hypertension, but the mechanisms are incompletely understood. To address this, we applied the 5/6th nephrectomy rat model to characterize hypertension and the response to dietary salt and renin-angiotensin inhibition. 5/6th nephrectomy caused low-renin, salt-sensitive hypertension with hyperkalemia and unsuppressed aldosterone. Compared to sham, 5/6Nx rats had lower NHE3, NKCC2, NCC, a-ENaC and Kir4.1, but higher SKG1, prostasin, g-ENaC, and Kir5.1. These differences correlated with plasma renin, aldosterone, and/or potassium. On a normal salt diet, adrenalectomy (0 ± 9 mmHg) and spironolactone (-11 ± 10 mmHg) prevented a progressive rise in blood pressure (10 ± 8 mmHg), and this was enhanced in combination with losartan (-41 ± 12 mmHg and -43 ± 9 mmHg). A high salt diet caused skin sodium and water accumulation and aggravated hypertension that could only be attenuated by spironolactone (-16 ± 7 mmHg) and in which the additive effect of losartan was lost. Spironolactone also increased natriuresis, reduced skin water accumulation and restored vasorelaxation. In summary, in the 5/6th nephrectomy rat CKD model, salt-sensitive hypertension develops with a selective increase in g-ENaC and despite appropriate transporter adaptations to low renin and hyperkalemia. With a normal salt diet, hypertension in 5/6th nephrectomy depends on angiotensin II and aldosterone, while a high salt diet causes more severe hypertension mediated through the mineralocorticoid receptor.

scholarly journals Endothelial cell transfusion ameliorates endothelial dysfunction in 5/6 nephrectomized rats

2013 ◽  
Vol 305 (8) ◽  
pp. H1256-H1264 ◽  
Author(s):  
Maricica Pacurari ◽  
Dongqi Xing ◽  
Rob H. P. Hilgers ◽  
Yuan Yuan Guo ◽  
Zhengqin Yang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Chronic Kidney Disease ◽  
Endothelial Dysfunction ◽  
Nitric Oxide Synthase ◽  
Kidney Disease ◽  
Endothelial Nitric Oxide Synthase ◽  
Vascular Function ◽  
Vascular Reactivity ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Endothelial dysfunction is prevalent in chronic kidney disease. This study tested the hypothesis that transfusion of rat aortic endothelial cells (ECs) ameliorates endothelial dysfunction in a rat model of chronic kidney disease. Male Sprague-Dawley rats underwent sham surgery or 5/6 nephrectomy (Nx). Five weeks after Nx, EC (1.5 × 106 cells/rat) or vehicle were transfused intravenously. One week later, vascular reactivity of mesenteric artery was assessed on a wire myograph. Sensitivity of endothelium-dependent relaxation to acetylcholine and maximum vasodilation were impaired by Nx and improved by EC transfusion. Using selective pharmacological nitric oxide synthase isoform inhibitors, we demonstrated that the negative effect of Nx on endothelial function and rescue by EC transfusion are, at least in part, endothelial nitric oxide synthase mediated. Plasma asymmetric dimethylarginine was increased by Nx and decreased by EC transfusion, whereas mRNA expression of dimethylarginine dimethylaminohydrolases 1 (DDAH1) was decreased by Nx and restored by EC transfusion. Immunohistochemical staining confirmed that local expression of DDAH1 is decreased by Nx and increased by EC transfusion. In conclusion, EC transfusion attenuates Nx-induced endothelium-dependent vascular dysfunction by regulating DDAH1 expression and enhancing endothelial nitric oxide synthase activity. These results suggest that EC-based therapy could provide a novel therapeutic strategy to improve vascular function in chronic kidney disease.

Endothelial nitric oxide synthase gene intron4 VNTR polymorphism in patients with chronic kidney disease

2011 ◽  
Vol 22 (6) ◽  
pp. 487-492 ◽  
Author(s):  
Manal F. Elshamaa ◽  
Samar Sabry ◽  
Ahmed Badr ◽  
Mostafa El-Ahmady ◽  
Eman A. Elghoroury ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Chronic Kidney Disease ◽  
Nitric Oxide Synthase ◽  
Kidney Disease ◽  
Endothelial Nitric Oxide Synthase ◽  
Vntr Polymorphism ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

scholarly journals The metabolic profile of a rat model of chronic kidney disease

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3352 ◽  
Author(s):  
Yohei Tanada ◽  
Junji Okuda ◽  
Takao Kato ◽  
Eri Minamino-Muta ◽  
Ichijiro Murata ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chronic Kidney Disease ◽  
Energy Metabolism ◽  
Kidney Disease ◽  
Rat Model ◽  
Elevated Serum ◽  
High Salt ◽  
Suitable Model ◽  
High Salt Diet ◽  
Salt Diet

BackgroundThe kidney is always subjected to high metabolic demand. The aim of this study was to characterize metabolic profiles of a rat model of chronic kidney disease (CKD) with cardiorenal syndrome (CRS) induced by prolonged hypertension.MethodsWe used inbred male Dahl salt-sensitive (DS) rats fed an 8% NaCl diet from six weeks of age (high-salt; HS group) or a 0.3% NaCl diet as controls (low-salt; LS group). We analyzed function, pathology, metabolome, and the gene expression related to energy metabolism of the kidney.ResultsDS rats with a high-salt diet showed hypertension at 11 weeks of age and elevated serum levels of creatinine and blood urea nitrogen with heart failure at 21 weeks of age. The fibrotic area in the kidneys increased at 21 weeks of age. In addition, gene expression related to mitochondrial function was largely decreased. The levels of citrate and isocitrate increased and the gene expression of alpha-ketoglutaratedehydrogenase and succinyl-CoA synthetase decreased; these are enzymes that metabolize citrate and isocitrate, respectively. In addition, the levels of succinate and acetyl Co-A, both of which are metabolites of the tricarboxylic acid (TCA) cycle, decreased.ConclusionsDS rats fed a high-salt diet were deemed a suitable model of CKD with CRS. Gene expression and metabolites related to energy metabolism and mitochondria in the kidney significantly changed in DS rats with hypertension in accordance with the progression of renal injury.

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