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 Dietary Phosphorus Differentially Alters Uremic Toxin Production in a Rat Model of Chronic Kidney Disease

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 843-843
Author(s):  
Dennis Cladis ◽  
Kendal Schmitz ◽  
Amber Jannasch ◽  
Bruce Cooper ◽  
Kathleen Hill Gallant
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Rat Model ◽  
Kidney Tissue ◽  
Toxin Production ◽  
Sham Operation ◽  
Uremic Toxin ◽  
Sprague Dawley ◽  
Waste Products ◽  
Dietary Phosphorus

Abstract Objectives Chronic kidney disease (CKD) is characterized by declining kidney function, limiting the kidney's ability to efficiently remove metabolic waste products from circulation. Byproducts of gut microbial protein metabolism, termed uremic retention solutes (URS), accumulate in CKD patients and are associated with accelerating kidney decline. The gut microbes responsible for generating URS are dependent upon phosphorus (P) for growth and survival. As dietary P restriction is a cornerstone of CKD treatment, we hypothesized that changes in dietary P loads would alter URS production. Methods To evaluate this, 8-week-old male Sprague Dawley rats underwent 5/6th nephrectomy (Nx, n = 24) or sham operation (n = 20) and were maintained on a 0.6% P diet (w/w) for three weeks. Animals were then randomized to receive either low (0.1% (w/w)) or high (1.2% (w/w)) P diets for 4h/d for 7d. Blood was collected at the start and end of the 7d diet (baseline and sacrifice, respectively). Serum was analyzed for blood urea nitrogen (BUN) and URS, including trimethylamine oxide (TMAO), indoxyl sulfate (IS), and p-cresol sulfate (pCS), via LC-MS. Results Nx rats had significantly elevated BUN compared to sham controls (38.9 ± 5.9 vs 23.1 ± 5.1 mg/dL, p < 0.0001). Additionally, the presence of significantly enlarged kidney tissue in Nx animals verified the progression of kidney decline. At sacrifice, all URS were elevated in Nx animals as compared to sham controls (p < 0.0001), though changes in dietary P loads only affected IS production (low vs. high, p = 0.0003). When comparing baseline to sacrifice, TMAO decreased, IS remained consistent, and pCS increased in all rats. Conclusions Our results indicate that dietary P loads may differentially affect the production of some URS in a rat model of CKD. As dietary P restriction is one of the cornerstones of CKD treatment, we posit that this dietary strategy influences URS production, CKD progression, and, ultimately, health outcomes. Funding Sources ASBMR, NIH K01.

scholarly journals A dual blocker of endothelin A/B receptors mitigates hypertension but not renal dysfunction in a rat model of chronic kidney disease and sleep apnea

2019 ◽  
Vol 316 (5) ◽  
pp. F1041-F1052 ◽  
Author(s):  
Humberto Morales-Loredo ◽  
David Jones ◽  
Adelaeda Barrera ◽  
Perenkita J. Mendiola ◽  
Joshua Garcia ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Sleep Apnea ◽  
Kidney Disease ◽  
Renal Dysfunction ◽  
Rat Model ◽  
Sprague Dawley ◽  
Arterial Blood ◽  
Sprague Dawley Rats ◽  
Obstructive Sleep ◽  
End Stage

Obstructive sleep apnea is characterized by recurrent episodes of pharyngeal collapse during sleep, resulting in intermittent hypoxia (IH), and is associated with a high incidence of hypertension and accelerated renal failure. In rodents, endothelin (ET)-1 contributes to IH-induced hypertension, and ET-1 levels inversely correlate with glomerular filtration rate in patients with end-stage chronic kidney disease (CKD). Therefore, we hypothesized that a dual ET receptor antagonist, macitentan (Actelion Pharmaceuticals), will attenuate and reverse hypertension and renal dysfunction in a rat model of combined IH and CKD. Male Sprague-Dawley rats received one of three diets (control, 0.2% adenine, and 0.2% adenine + 30 mg·kg−1·day−1macitentan) for 2 wk followed by 2 wk of recovery diet. Rats were then exposed for 4 wk to air or IH (20 short exposures/h to 5% O2-5% CO27 h/day during sleep). Macitentan prevented the increases in mean arterial blood pressure caused by CKD, IH, and the combination of CKD + IH. However, macitentan did not improve kidney function, fibrosis, and inflammation. After CKD was established, rats were exposed to air or IH for 2 wk, and macitentan feeding continued for 2 more wk. Macitentan reversed the hypertension in IH, CKD, and CKD + IH groups without improving renal function. Our data suggest that macitentan could be an effective antihypertensive in patients with CKD and irreversible kidney damage as a way to protect the heart, brain, and eyes from elevated arterial pressure, but it does not reverse toxin-induced tubule atrophy.

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.

Renal endothelin in chronic angiotensin II hypertension

2002 ◽  
Vol 283 (1) ◽  
pp. R243-R248 ◽  
Author(s):  
Jennifer M. Sasser ◽  
Jennifer S. Pollock ◽  
David M. Pollock
Keyword(s):  
Sodium Intake ◽  
Renal Tissue ◽  
High Salt ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Outer Medulla ◽  
High Salt Diet ◽  
Salt Diet ◽  
Sprague Dawley Rats ◽  
Saline Vehicle

To determine the influence of chronic ANG II infusion on urinary, plasma, and renal tissue levels of immunoreactive endothelin (ET), ANG II (65 ng/min) or saline vehicle was delivered via osmotic minipump in male Sprague-Dawley rats given either a high-salt diet (10% NaCl) or normal-salt diet (0.8% NaCl). High-salt diet alone caused a slight but not statistically significant increase (7 ± 1%) in mean arterial pressure (MAP). MAP was significantly increased in ANG II-infused rats (41 ± 10%), and the increase in MAP was significantly greater in ANG II rats given a high-salt diet (59 ± 1%) compared with the increase observed in rats given a high-salt diet alone or ANG II infusion and normal-salt diet. After a 2-wk treatment, urinary excretion of immunoreactive ET was significantly increased by ∼50% in ANG II-infused animals and by over 250% in rats on high-salt diet, with or without ANG II infusion. ANG II infusion combined with high-salt diet significantly increased immunoreactive ET content in the cortex and outer medulla, but this effect was not observed in other groups. In contrast, high-salt diet, with or without ANG II infusion, significantly decreased immunoreactive ET content within the inner medulla. These data indicate that chronic elevations in ANG II levels and sodium intake differentially affect ET levels within the kidney and provide further support for the hypothesis that the hypertensive effects of ANG II may be due to interaction with the renal ET system.

scholarly journals Aortic Stiffness and Diastolic Dysfunction in Sprague Dawley Rats Consuming Short-Term Fructose Plus High Salt Diet

2020 ◽  
Vol Volume 13 ◽  
pp. 111-124
Author(s):  
Dragana Komnenov ◽  
Peter E Levanovich ◽  
Natalia Perecki ◽  
Charles S Chung ◽  
Noreen F Rossi
Keyword(s):  
Diastolic Dysfunction ◽  
Aortic Stiffness ◽  
High Salt ◽  
Sprague Dawley ◽  
Short Term ◽  
High Salt Diet ◽  
Salt Diet ◽  
Sprague Dawley Rats

scholarly journals Fructose plus High-Salt Diet in Early Life Results in Salt-Sensitive Cardiovascular Changes in Mature Male Sprague Dawley Rats

Nutrients ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 3129
Author(s):  
Peter E. Levanovich ◽  
Charles S. Chung ◽  
Dragana Komnenov ◽  
Noreen F. Rossi
Keyword(s):  
Phase I ◽  
Left Ventricular ◽  
High Salt ◽  
Male Rats ◽  
Phase Iii ◽  
Lv Function ◽  
Sprague Dawley ◽  
High Salt Diet ◽  
Salt Diet ◽  
Sprague Dawley Rats

Fructose and salt intake remain high, particularly in adolescents and young adults. The present studies were designed to evaluate the impact of high fructose and/or salt during pre- and early adolescence on salt sensitivity, blood pressure, arterial compliance, and left ventricular (LV) function in maturity. Male 5-week-old Sprague Dawley rats were studied over three 3-week phases (Phases I, II, and III). Two reference groups received either 20% glucose + 0.4% NaCl (GCS-GCS) or 20% fructose + 4% NaCl (FHS-FHS) throughout this study. The two test groups ingested fructose + 0.4% NaCl (FCS) or FHS during Phase I, then GCS in Phase II, and were then challenged with 20% glucose + 4% NaCl (GHS) in Phase III: FCS-GHS and FHS-GHS, respectively. Compared with GCS-GCS, systolic and mean pressures were significantly higher at the end of Phase III in all groups fed fructose during Phase I. Aortic pulse wave velocity (PWV) was elevated at the end of Phase I in FHS-GHS and FHS-FHS (vs. GCS-GCS). At the end of Phase III, PWV and renal resistive index were higher in FHS-GHS and FHS-FHS vs. GCS-GCS. Diastolic, but not systolic, LV function was impaired in the FHS-GHS and FHS-FHS but not FCS-FHS rats. Consumption of 20% fructose by male rats during adolescence results in salt-sensitive hypertension in maturity. When ingested with a high-salt diet during this early plastic phase, dietary fructose also predisposes to vascular stiffening and LV diastolic dysfunction in later life.

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