scholarly journals Rag1-null Dahl SS rats reveal that adaptive immune mechanisms exacerbate high protein-induced hypertension and renal injury

2018 ◽  
Vol 315 (1) ◽  
pp. R28-R35 ◽  
Author(s):  
Justine M. Abais-Battad ◽  
Hayley Lund ◽  
Daniel J. Fehrenbach ◽  
John Henry Dasinger ◽  
David L. Mattson
Keyword(s):  
B Lymphocytes ◽  
Dietary Protein ◽  
High Protein Diet ◽  
High Salt ◽  
High Protein ◽  
Protein Diet ◽  
High Salt Diet ◽  
Salt Diet ◽  
Adaptive Immune ◽  
Induced Hypertension

The present study, performed in Dahl salt-sensitive (SS) and SS- Rag1−/− rats lacking T and B lymphocytes, tested the hypothesis that immune cells amplify salt-sensitive hypertension and kidney damage in response to a high-protein diet. After being weaned, SS and SS- Rag1−/− rats were placed on an isocaloric, 0.4% NaCl diet containing normal (18%) or high (30%) protein. At 9 wk of age, rats were switched to a 4.0% NaCl diet containing the same amount of dietary protein and maintained on the high-salt diet for 3 wk. After being fed the high-salt diet, SS rats fed high protein had amplified hypertension and albumin excretion (158.7 ± 2.6 mmHg and 140.8 ± 16.0 mg/day, respectively, means ± SE) compared with SS rats fed normal protein (139.4 ± 3.6 mmHg and 69.4 ± 11.3 mg/day). When compared with the SS rats, SS- Rag1−/− rats fed high protein were protected from exacerbated hypertension and albuminuria (142.9 ± 5.8 mmHg and 66.2 ± 10.8 mg/day). After 3 wk of the high-salt diet, there was a corresponding increase in total leukocyte infiltration (CD45+) in the kidneys of both strains fed high-protein diet. The SS- Rag1−/− rats fed high-protein diet had 74–86% fewer CD3+ T lymphocytes and CD45R+ B lymphocytes infiltrating the kidney versus SS rats, but there was no difference in the infiltration of CD11b/c+ monocytes and macrophages, suggesting that the protective effects observed in the SS- Rag1−/− rats are specific to the reduction of lymphocytes. With the SS- Rag1−/− rats utilized as a novel tool to explore the effects of lymphocyte deficiency, these results provide evidence that adaptive immune mechanisms contribute to the exacerbation of salt-induced hypertension and renal injury mediated by increased dietary protein intake.

Urea and inulin clearances in undisturbed, unanesthetized rats

1965 ◽  
Vol 208 (3) ◽  
pp. 578-584 ◽  
Author(s):  
Leonard I. Kleinman ◽  
Edward P. Radford ◽  
Giorgio Torelli
Keyword(s):  
Salt Content ◽  
High Protein Diet ◽  
High Salt ◽  
High Protein ◽  
The Other ◽  
Protein Diet ◽  
Inulin Clearance ◽  
Chow Diet ◽  
High Salt Diet ◽  
Salt Diet

Inulin and urea clearances were determined simultaneously on unanesthetized, undisturbed rats with catheters permanently inserted in the abdominal aorta, jugular vein, and urinary bladder. The rats were fed a) a normal Purina chow diet; b) a high-protein diet with normal salt content; or c) a high-protein diet with 2% NaCl added. Some rats on the high-protein, high-salt diet were given additional infusions of either urea or 5% amino acid solution. In the control animals, inulin clearances averaged 0.59 ml/min per 100 g body wt, and urea clearances averaged 0.39 ml/min per 100 g body wt. Significantly higher urea and inulin clearances were obtained on the other diets. Of 79 clearances determined on normal rats given the high-protein, high-salt diet, a total of 17 urea-to-inulin clearance ratios greater than one were obtained No urea-to-inulin clearance ratios greater than one were obtained with any of the other diets. Reasons are given in support of urea production or active secretion by the kidneys as the probable explanations for these results.

Overload proteinuria is followed by salt-sensitive hypertension caused by renal infiltration of immune cells

2002 ◽  
Vol 283 (5) ◽  
pp. F1132-F1141 ◽  
Author(s):  
Violeta Alvarez ◽  
Yasmir Quiroz ◽  
Mayerly Nava ◽  
Héctor Pons ◽  
Bernardo Rodríguez-Iturbe
Keyword(s):  
Interstitial Nephritis ◽  
Renal Damage ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Malondialdehyde Content ◽  
Induced Hypertension ◽  
Salt Sensitive Hypertension ◽  
And Control ◽  
And Oxidative Stress

Recent evidence suggests that salt-sensitive hypertension develops as a consequence of renal infiltration with immunocompetent cells. We investigated whether proteinuria, which is known to induce interstitial nephritis, causes salt-sensitive hypertension. Female Lewis rats received 2 g of BSA intraperitoneally daily for 2 wk. After protein overload (PO), 6 wk of a high-salt diet induced hypertension [systolic blood pressure (SBP) = 156 ± 11.8 mmHg], whereas rats that remained on a normal-salt diet and control rats (without PO) on a high-salt diet were normotensive. Administration of mycophenolate mofetil (20 mg · kg−1 · day−1) during PO resulted in prevention of proteinuria-related interstitial nephritis, reduction of renal angiotensin II-positive cells and oxidative stress (superoxide-positive cells and renal malondialdehyde content), and resistance to the hypertensive effect of the high-salt diet (SBP = 129 ± 12.2 mmHg). The present studies support the participation of renal inflammatory infiltrate in the pathogenesis of salt-sensitive hypertension and provide a direct link between two risk factors of progressive renal damage: proteinuria and hypertension.

scholarly journals Intestinal Flora Modulates Blood Pressure by Regulating the Synthesis of Intestinal-Derived Corticosterone in High Salt-Induced Hypertension

2020 ◽  
Vol 126 (7) ◽  
pp. 839-853 ◽  
Author(s):  
Xuefang Yan ◽  
Jiajia Jin ◽  
Xinhuan Su ◽  
Xianlun Yin ◽  
Jing Gao ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Arachidonic Acid ◽  
Fecal Microbiota Transplantation ◽  
Intestinal Flora ◽  
Corticosterone Level ◽  
Fecal Microbiota ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Induced Hypertension

Rationale: High-salt diet is one of the most important risk factors for hypertension. Intestinal flora has been reported to be associated with high salt–induced hypertension (hSIH). However, the detailed roles of intestinal flora in hSIH pathogenesis have not yet been fully elucidated. Objective: To reveal the roles and mechanisms of intestinal flora in hSIH development. Methods and Results: The abovementioned issues were investigated using various techniques including 16S rRNA gene sequencing, untargeted metabolomics, selective bacterial culture, and fecal microbiota transplantation. We found that high-salt diet induced hypertension in Wistar rats. The fecal microbiota of healthy rats could dramatically lower blood pressure (BP) of hypertensive rats, whereas the fecal microbiota of hSIH rats had opposite effects. The composition, metabolism, and interrelationship of intestinal flora in hSIH rats were considerably reshaped, including the increased corticosterone level and reduced Bacteroides and arachidonic acid levels, which tightly correlated with BP. The serum corticosterone level was also significantly increased in rats with hSIH. Furthermore, the above abnormalities were confirmed in patients with hypertension. The intestinal Bacteroides fragilis could inhibit the production of intestinal-derived corticosterone induced by high-salt diet through its metabolite arachidonic acid. Conclusions: hSIH could be transferred by fecal microbiota transplantation, indicating the pivotal roles of intestinal flora in hSIH development. High-salt diet reduced the levels of B fragilis and arachidonic acid in the intestine, which increased intestinal-derived corticosterone production and corticosterone levels in serum and intestine, thereby promoting BP elevation. This study revealed a novel mechanism different from inflammation/immunity by which intestinal flora regulated BP, namely intestinal flora could modulate BP by affecting steroid hormone levels. These findings enriched the understanding of the function of intestinal flora and its effects on hypertension.

scholarly journals Characterization of homocysteine metabolism in the rat liver

2000 ◽  
Vol 350 (3) ◽  
pp. 685-692 ◽  
Author(s):  
Lori M. STEAD ◽  
Margaret E. BROSNAN ◽  
John T. BROSNAN
Keyword(s):  
Amino Acid ◽  
Dietary Protein ◽  
High Protein Diet ◽  
Plasma Homocysteine ◽  
High Protein ◽  
Protein Diet ◽  
Total Plasma ◽  
Methionine Concentration ◽  
Protein Group

Recent evidence suggests that an increased plasma concentration of the sulphur amino acid homocysteine is a risk factor for the development of vascular disease. The tissue(s) responsible for homocysteine production and export to the plasma are not well known. However, given the central role of the liver in amino acid metabolism, we developed a rat primary hepatocyte model in which homocysteine (and cysteine) production and export were examined. The dependence of homocysteine export from incubated hepatocytes on methionine concentration fitted well to a rectangular hyperbola, with half-maximal homocysteine export achieved at methionine concentrations of approx. 0.44mM. Hepatocytes incubated with 1mM methionine and 1mM serine (a substrate for the transulphuration pathway of homocysteine removal) produced and exported significantly less homocysteine (25–40%) compared with cells incubated with 1mM methionine alone. The effects of dietary protein on homocysteine metabolism were also examined. Rats fed a 60% protein diet had a significantly increased total plasma homocysteine level compared with rats fed a 20% protein diet. Invitro effects of dietary protein were examined using hepatocytes isolated from animals maintained on these diets. When incubated with 1mM methionine, hepatocytes from rats fed the high protein diet exported significantly more homocysteine compared with hepatocytes from rats fed the normal protein diet. Inclusion of serine significantly lowered homocysteine export in the normal protein group, but the effect was more marked in the high protein group. Invivo effects of serine were also examined. Rats fed a high protein diet enriched with serine had significantly lower total plasma homocysteine (25–30%) compared with controls. These data indicate a significant role for the liver in the regulation of plasma homocysteine levels.

scholarly journals Role of central nervous system aldosterone synthase and mineralocorticoid receptors in salt-induced hypertension in Dahl salt-sensitive rats

2009 ◽  
Vol 296 (4) ◽  
pp. R994-R1000 ◽  
Author(s):  
Bing S. Huang ◽  
Roselyn A. White ◽  
Arco Y. Jeng ◽  
Frans H. H. Leenen
Keyword(s):  
Salt Intake ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Aldosterone Synthase ◽  
High Salt Intake ◽  
Induced Hypertension ◽  
Synthase Inhibitor ◽  
The Brain

In Dahl salt-sensitive (S) rats, high salt intake increases cerebrospinal fluid (CSF) Na+ concentration ([Na+]) and blood pressure (BP). Intracerebroventricular (ICV) infusion of a mineralocorticoid receptor (MR) blocker prevents the hypertension. To assess the role of aldosterone locally produced in the brain, we evaluated the effects of chronic central blockade with the aldosterone synthase inhibitor FAD286 and the MR blocker spironolactone on changes in aldosterone and corticosterone content in the hypothalamus and the increase in CSF [Na+] and hypertension induced by high salt intake in Dahl S rats. After 4 wk of high salt intake, plasma aldosterone and corticosterone were not changed, but hypothalamic aldosterone increased by ∼35% and corticosterone tended to increase in Dahl S rats, whereas both steroids decreased by ∼65% in Dahl salt-resistant rats. In Dahl S rats fed the high-salt diet, ICV infusion of FAD286 or spironolactone did not affect the increase in CSF [Na+]. ICV infusion of FAD286 prevented the increase in hypothalamic aldosterone and 30 mmHg of the 50-mmHg BP increase induced by high salt intake. ICV infusion of spironolactone fully prevented the salt-induced hypertension. These results suggest that, in Dahl S rats, high salt intake increases aldosterone synthesis in the hypothalamus and aldosterone acts as the main MR agonist activating central pathways contributing to salt-induced hypertension.

Melatonin prevents kidney injury in a high salt diet-induced hypertension model by decreasing oxidative stress

2015 ◽  
Vol 60 (1) ◽  
pp. 48-54 ◽  
Author(s):  
Avshalom Leibowitz ◽  
Alexander Volkov ◽  
Konstantin Voloshin ◽  
Chen Shemesh ◽  
Iris Barshack ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Kidney Injury ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Induced Hypertension

scholarly journals Alamandine alleviates hypertension and renal damage via oxidative-stress attenuation in Dahl rats

2022 ◽  
Vol 8 (1) ◽  
Author(s):  
Juexiao Gong ◽  
Man Luo ◽  
Yonghong Yong ◽  
Shan Zhong ◽  
Peng Li
Keyword(s):  
Oxidative Stress ◽  
Renal Dysfunction ◽  
Renal Damage ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Renal Tubular Cells ◽  
Induced Hypertension

AbstractAlamandine (Ala) is a novel member of the renin–angiotensin-system (RAS) family. The present study aimed to explore the effects of Ala on hypertension and renal damage of Dahl salt-sensitive (SS) rats high-salt diet-induced, and the mechanisms of Ala on renal-damage alleviation. Dahl rats were fed with high-salt diets to induce hypertension and renal damage in vivo, and HK-2 cells were treated with sodium chloride (NaCl) to induce renal injury in vitro. Ala administration alleviated the high-salt diet-induced hypertension, renal dysfunction, and renal fibrosis and apoptosis in Dahl SS rats. The HK-2 cells’ damage, and the increases in the levels of cleaved (c)-caspase3, c-caspase8, and c-poly(ADP-ribose) polymerase (PARP) induced by NaCl were inhibited by Ala. Ala attenuated the NaCl-induced oxidative stress in the kidney and HK-2 cells. DETC, an inhibitor of SOD, reversed the inhibitory effect of Ala on the apoptosis of HK-2 cells induced by NaCl. The NaCl-induced increase in the PKC level was suppressed by Ala in HK-2 cells. Notably, PKC overexpression reversed the moderating effects of Ala on the NaCl-induced apoptosis of HK-2 cells. These results show that Ala alleviates high-salt diet-induced hypertension and renal dysfunction. Ala attenuates the renal damage via inhibiting the PKC/reactive oxygen species (ROS) signaling pathway, thereby suppressing the apoptosis in renal tubular cells.

scholarly journals Dietary Protein Intake Level Modulates Mucosal Healing and Mucosa-Adherent Microbiota in Mouse Model of Colitis

Nutrients ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 514 ◽  
Author(s):  
Sandra Vidal-Lletjós ◽  
Mireille Andriamihaja ◽  
Anne Blais ◽  
Marta Grauso ◽  
Patricia Lepage ◽  
...  
Keyword(s):  
Dietary Protein ◽  
Protein Intake ◽  
High Protein Diet ◽  
Repair Process ◽  
Mucosal Healing ◽  
High Protein ◽  
Protein Diet ◽  
Dietary Protein Intake ◽  
Epithelial Repair ◽  
The Impact

Mucosal healing after an inflammatory flare is associated with lasting clinical remission. The aim of the present work was to evaluate the impact of the amount of dietary protein on epithelial repair after an acute inflammatory episode. C57BL/6 DSS-treated mice received isocaloric diets with different levels of dietary protein: 14% (P14), 30% (P30) and 53% (P53) for 3 (day 10), 6 (day 13) and 21 (day 28) days after the time of colitis maximal intensity. While the P53 diet worsened the DSS- induced inflammation both in intensity and duration, the P30 diet, when compared to the P14 diet, showed a beneficial effect during the epithelial repair process by accelerating inflammation resolution, reducing colonic permeability and increasing epithelial repair together with epithelial hyperproliferation. Dietary protein intake also impacted mucosa-adherent microbiota composition after inflammation since P30 fed mice showed increased colonization of butyrate-producing genera throughout the resolution phase. This study revealed that in our colitis model, the amount of protein in the diet modulated mucosal healing, with beneficial effects of a moderately high-protein diet, while very high-protein diet displayed deleterious effects on this process.

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