Calcitriol ameliorates damage in high-salt diet-induced hypertension: Evidence of communication with the gut–kidney axis

2021 ◽  
pp. 153537022110625
Author(s):  
Ruifeng Ding ◽  
Zilong Xiao ◽  
Yufeng Jiang ◽  
Yi Yang ◽  
Yang Ji ◽  
...  
Keyword(s):  
Vitamin D ◽  
Gut Microbiota ◽  
Intestinal Flora ◽  
Intestinal Barrier ◽  
Vitamin D Supplementation ◽  
High Salt ◽  
Intestinal Barrier Function ◽  
High Salt Diet ◽  
Salt Diet ◽  
Induced Hypertension

Several studies have established a link between high-salt diet, inflammation, and hypertension. Vitamin D supplementation has shown anti-inflammatory effects in many diseases; gut microbiota is also associated with a wide variety of cardiovascular diseases, but potential role of vitamin D and gut microbiota in high-salt diet-induced hypertension remains unclear. Therefore, we used rats with hypertension induced by a high-salt diet as the research object and analyzed the transcriptome of their tissues (kidney and colon) and gut microbiome to conduct an overall analysis of the gut–kidney axis. We aimed to confirm the effects of high salt and calcitriol on the gut–kidney immune system and the composition of the intestinal flora. We demonstrate that consumption of a high-salt diet results in hypertension and inflammation in the colon and kidney and alteration of gut microbiota composition and function. High-salt diet-induced hypertension was found to be associated with seven microbial taxa and mainly associated with reduced production of the protective short-chain fatty acid butyrate. Calcitriol can reduce colon and kidney inflammation, and there are gene expression changes consistent with restored intestinal barrier function. The protective effect of calcitriol may be mediated indirectly by immunological properties. Additionally, the molecular pathways of the gut microbiota-mediated blood pressure regulation may be related to circadian rhythm signals, which needs to be further investigated. An innovative association analysis of the microbiota may be a key strategy to understanding the association between gene patterns and host.

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.

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 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.

Effect of salt-induced hypertension on microvascular pressures in skeletal muscle of Dahl rats

1991 ◽  
Vol 260 (6) ◽  
pp. H1819-H1825 ◽  
Author(s):  
M. A. Boegehold
Keyword(s):  
Skeletal Muscle ◽  
Pressure Drop ◽  
Pressure Profile ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Small Arteries ◽  
Induced Hypertension ◽  
High Hydrostatic Pressures ◽  
Made In

The purpose of this study was to determine the effect of salt-induced hypertension on the microvascular pressure profile in skeletal muscle. Measurements were made in the spinotrapezius muscle of anesthetized Dahl salt-sensitive (DS) rats fed either a high- (7%) or low-normal (0.45%)-NaCl diet for 4 wk. Age-matched Dahl salt-resistant (DR) rats on high- or low-normal salt diets were also studied. The high-salt diet had no effect on either arterial or microvascular pressures in DR rats. DS rats maintained on high salt developed arterial hypertension accompanied by a pressure increase of 49% in the feed arterioles and 31% in the transverse arterioles. Hypertensive DS rats exhibited a greater pressure drop across the small arteries, arcade arterioles, and distal arterioles, indicating that each of these segments contributes to increased whole organ resistance. Pressures in the collecting and draining venules were not elevated in DS on 7% NaCl, suggesting that increased precapillary resistance in salt-induced hypertension effectively shields the skeletal muscle capillary and venular networks from high hydrostatic pressures.

Su1901 High Salt Diet Increases Susceptibility to Experimental Colitis: A Putative Role of Gut Microbiota

2016 ◽  
Vol 150 (4) ◽  
pp. S583 ◽  
Author(s):  
Pedro M. Miranda ◽  
Viktoria Serkis ◽  
Giada de Palma ◽  
Marc Pigrau ◽  
Jun Lu ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Experimental Colitis ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Putative Role

scholarly journals Myocardial energetics is not compromised during compensated hypertrophy in the Dahl salt-sensitive rat model of hypertension

2016 ◽  
Vol 311 (3) ◽  
pp. H563-H571 ◽  
Author(s):  
Kenneth Tran ◽  
June-Chiew Han ◽  
Andrew J. Taberner ◽  
Carolyn J. Barrett ◽  
Edmund J. Crampin ◽  
...  
Keyword(s):  
Mechanical Efficiency ◽  
Left Ventricular ◽  
High Salt ◽  
Shortening Velocity ◽  
High Salt Diet ◽  
Salt Diet ◽  
Hypertrophic Response ◽  
Induced Hypertension ◽  
Myocardial Energetics ◽  
Work Loop

Salt-induced hypertension leads to development of left ventricular hypertrophy in the Dahl salt-sensitive (Dahl/SS) rat. Before progression to left ventricular failure, the heart initially undergoes a compensated hypertrophic response. We hypothesized that changes in myocardial energetics may be an early indicator of transition to failure. Dahl/SS rats and their salt-resistant consomic controls (SS-13BN) were placed on either a low- or high-salt diet to generate four cohorts: Dahl-SS rats on a low- (Dahl-LS) or high-salt diet (Dahl-HS), and SS-13BN rats on a low- (SSBN-LS) or high-salt diet (SSBN-HS). We isolated left ventricular trabeculae and characterized their mechanoenergetic performance. Our results show, at most, modest effects of salt-induced compensated hypertrophy on myocardial energetics. We found that the Dahl-HS cohort had a higher work-loop heat of activation (estimated from the intercept of the heat vs. relative afterload relationship generated from work-loop contractions) relative to the SSBN-HS cohort and a higher economy of contraction (inverse of the slope of the heat vs. active stress relation) relative to the Dahl-LS cohort. The maximum extent of shortening and maximum shortening velocity of the Dahl/SS groups were higher than those of the SS-13BN groups. Despite these differences, no significant effect of salt-induced hypertension was observed for either peak work output or peak mechanical efficiency during compensated hypertrophy.

scholarly journals High Na+ Salt Diet and Remodeling of Vascular Smooth Muscle and Endothelial Cells

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 883
Author(s):  
Ghassan Bkaily ◽  
Yanick Simon ◽  
Ashley Jazzar ◽  
Houssein Najibeddine ◽  
Alexandre Normand ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Smooth Muscle ◽  
High Salt ◽  
Vascular Endothelial ◽  
High Cardiovascular Risk ◽  
High Salt Diet ◽  
Salt Diet ◽  
Lower Survival Rate ◽  
High Sodium ◽  
Induced Hypertension

Our knowledge on essential hypertension is vast, and its treatment is well known. Not all hypertensives are salt-sensitive. The available evidence suggests that even normotensive individuals are at high cardiovascular risk and lower survival rate, as blood pressure eventually rises later in life with a high salt diet. In addition, little is known about high sodium (Na+) salt diet-sensitive hypertension. There is no doubt that direct and indirect Na+ transporters, such as the Na/Ca exchanger and the Na/H exchanger, and the Na/K pump could be implicated in the development of high salt-induced hypertension in humans. These mechanisms could be involved following the destruction of the cell membrane glycocalyx and changes in vascular endothelial and smooth muscle cells membranes’ permeability and osmolarity. Thus, it is vital to determine the membrane and intracellular mechanisms implicated in this type of hypertension and its treatment.

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