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.

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.

Contribution of volume overload to progression of cardiovascular disease in a rat model of chronic kidney disease

2018 ◽  
Vol 96 (12) ◽  
pp. 1197-1208
Author(s):  
Manal Moustafa Mahmoud ◽  
Asmaa Mohammed Shamseldeen ◽  
Laila Ahmed Rashed ◽  
Amal Elham Fares ◽  
Ashraf Shamaa ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Rat Model ◽  
Volume Overload ◽  
High Salt ◽  
Sham Operation ◽  
Sprague Dawley ◽  
High Salt Diet ◽  
Sprague Dawley Rats ◽  
Cardiac Functions

Volume overload is a common phenomenon in patients with chronic kidney disease that is associated with cardiovascular risk factors. However, its contribution to the development of adverse cardiovascular outcomes in those patients is not fully understood. Thus, the present work investigated the effect of salt-induced volume overload on cardiac functions and geometry in a rat model of chronic kidney disease. Thirty adult male Sprague–Dawley rats were randomly divided. One set of animals received a sham operation, while another set of animals underwent uninephrectomy. Rats were then fed either a normal-salt (0.4%) or high-salt (8.0%) diet for 6 weeks. The salt-loaded, uninephrectomized rats were treated with indapamide (3 mg·kg–1·day–1, orally) for 6 weeks. We found that uninephrectomized rats subjected to a high-salt diet (8.0%) for 6 weeks presented with hypertension, proteinuria, decreased renal Klotho expression, and deterioration in cardiac hemodynamics and histology. Echocardiography to assess cardiac function showed that ejection fraction and fractional shortening were positively correlated with relative renal Klotho expression. In conclusion, salt-induced volume overload in a rat model of chronic kidney disease has an adverse cardiovascular outcome and is associated with inflammatory activation and decrease in renal Klotho expression.

scholarly journals Fetal programming effects of pentaerythritol tetranitrate in a rat model of superimposed preeclampsia

2020 ◽  
Vol 98 (9) ◽  
pp. 1287-1299
Author(s):  
Andy W. C. Man ◽  
Min Chen ◽  
Yawen Zhou ◽  
Zhixiong Wu ◽  
Gisela Reifenberg ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Glucose Tolerance ◽  
Fetal Growth ◽  
Rat Model ◽  
High Salt ◽  
Pentaerythritol Tetranitrate ◽  
High Salt Diet ◽  
Blood Pressure Elevation ◽  
Salt Diet ◽  
Normal Chow

Abstract Preeclampsia is a common medical condition during pregnancy and a major cause of maternal and prenatal mortality. The present study was conducted to investigate the effects of maternal treatment with pentaerythritol tetranitrate (PETN) in Dahl salt-sensitive rats (DSSR), a model of superimposed preeclampsia. F0 parental DSSR were treated with PETN (50 mg/kg) from the time point of mating to the end of lactation. Maternal PETN treatment improved fetal growth and had no effect on blood pressure in DSSR offspring fed with normal chow or high-salt diet. Upon high-fat diet (HFD) feeding, offspring from PETN-treated mother showed improved glucose tolerance despite similar weight gain. Unexpectedly, maternal PETN treatment significantly potentiated the HFD-induced blood pressure elevation in male DSSR offspring. Endothelium-derived hyperpolarization factor (EDHF)-mediated vasodilation was similar between NCD-fed and HFD-fed control offspring but was markedly reduced in HFD-fed PETN offspring. EDHF genes were downregulated in the vasculature of HFD-fed PETN offspring, which was associated with epigenetic changes in histone modifications. In conclusion, maternal PETN treatment in DSSR shows both beneficial and unfavorable effects. It improves fetal growth and ameliorates glucose tolerance in the offspring. Although maternal PETN treatment has no effect on blood pressure in offspring fed with normal chow or high-salt diet, the offspring is at higher risk to develop HFD-induced hypertension. PETN may potentiate the blood pressure response to HFD by epigenetic modifications of EDHF genes. Key messages The core findings of this article suggest that maternal PETN treatment of DSSR, a rat model of a spontaneous superimposed preeclampsia, leads to • Improvement of fetal growth; • No changes of maternal blood pressure or markers of preeclampsia; • Amelioration of HFD-induced glucose intolerance in adult offspring; • No changes in blood pressure development of the offspring on normal chow or high salt-diet; • Potentiation of blood pressure elevation of the offspring on HFD.

The effects of a high salt diet on gene expression of Na+/H+ exchanger and growth factors in 5/6-nephrectomized rats

Nephrology ◽  
1998 ◽  
Vol 4 (3) ◽  
pp. 187-193
Author(s):  
Harumichi HIGASHI ◽  
Seiya OKUDA ◽  
Kiyoshi TAMAKI ◽  
Takashi ANDO ◽  
Masatoshi FUJISHIMA
Keyword(s):  
Gene Expression ◽  
Growth Factors ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet

scholarly journals High‐salt diet promotes crystal deposition through hypertension in Dahl salt‐sensitive rat model

2019 ◽  
Vol 26 (8) ◽  
pp. 839-846 ◽  
Author(s):  
Yusuke Nakazawa ◽  
Shinya Inoue ◽  
Yuka Nakamura ◽  
Yasuo Iida ◽  
Yasuhito Ishigaki ◽  
...  
Keyword(s):  
Rat Model ◽  
High Salt ◽  
Crystal Deposition ◽  
High Salt Diet ◽  
Salt Diet

scholarly journals High salt-diet reduces SLC14A1 gene expression in the choroid plexus of Dahl salt sensitive rats

2015 ◽  
Vol 461 (2) ◽  
pp. 254-259 ◽  
Author(s):  
Lirong Guo ◽  
Jie Meng ◽  
Chengluan Xuan ◽  
Jingyan Ge ◽  
Wenzhu Sun ◽  
...  
Keyword(s):  
Gene Expression ◽  
Choroid Plexus ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet

scholarly journals High salts intake, cardiovascular system and kidney in spontaneous hypertensive rats

2017 ◽  
Vol 16 (3) ◽  
pp. 62-69
Author(s):  
A. G. Kucher ◽  
O. N. Beresneva ◽  
M. M. Parastaeva ◽  
G. T. Ivanova ◽  
M. I. Zarajsky ◽  
...  
Keyword(s):  
Gene Expression ◽  
Blood Pressure ◽  
Heart Rate ◽  
Cardiovascular System ◽  
High Salt ◽  
Myocardial Remodeling ◽  
Hypertensive Rats ◽  
Relative Level ◽  
High Salt Diet ◽  
Salt Diet

Objective. To study the influence of diet containing high or normal NaCl on the arterial blood pressure level (BP), heart rate (HR), processes of myocardial remodeling and of nuclear transcription factor kB (NFkB) expression in myocardium and kidney in spontaneously hypertensive rats (SHR). Design and methods. The two groups of male SHRs received a diet with normal (0.34 %; n = 24, control) and high content of NaCl (8.0 %; n = 25; experimental group) for 2 months. Blood pressure (BP), heart rate (HR), cardiac left ventricular mass index (LVMI), left (LKMI) and right (RKMI) kidney mass indexes were determined. Morphological study of myocardium (light microscopy), including quantitative morphometry was carried out. In part of animals the relative level of NFkB gene expression in heart and kidney tissues was studied. Results and discussion. In rats fed a diet containing 8 % NaCl BP and HR did not change significantly compared with the control. However, LVMI, RKMI, LKMI were significantly higher in high-salt diet-treated animals than in controls. The heart of high-salt diet-treated animals developed the changes leading to hypertrophy and possibly hyperplasia of cardiomyocytes. In these animals, perivascular fibrosis, significant increase of arterial wall thickness and vacuolization of smooth muscle cells were revealed. The relative level of NFKB gene expression in rats receiving high-salt diet was 33-fold higher in myocardium and 12-fold higher in kidneys than in animals fed a normal salt diet. Conclusion. The high-salt diet is not necessarily accompanied by an increase in blood pressure, but causes myocardial remodeling, apparently due to direct «toxic» effects. The negative impact on the cardiovascular system of high-salt diet is in part mediated through NFkB-associated signaling pathways. Furthermore, high NaCl diet causes activation of NFkB in the kidneys.

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