Abstract 451: Depletion of Macrophage Prevents Exacerbated Renal Injury and Hypertension Induced by Degeneration of Trpv1-positive Nerves in Rats Subjected to Renal Ischemic Reperfusion and Salt Load

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Shuang-Quan Yu ◽  
Donna H Wang
Keyword(s):  
Renal Injury ◽  
Salt Intake ◽  
Ischemia Reperfusion ◽  
Tissue Growth ◽  
High Salt ◽  
Macrophage Infiltration ◽  
Transient Receptor Potential Vanilloid ◽  
Plasma Urea ◽  
Renal Inflammation ◽  
High Salt Intake

High salt intake after recovery from renal ischemia-reperfusion (I/R) injury leads to hypertension and renal inflammation. This study tests the hypothesis that degeneration of transient receptor potential vanilloid type 1 (TRPV1)-positive nerves exacerbates salt-induced hypertension and renal inflammation after I/R via enhancing renal macrophage infiltration. Rats were fed a low sodium (0.4%) diet for 5 weeks after capsaicin pre-treatment (CAP, 100 mg/kg, s.c.) and renal I/R, followed by macrophage depletion with clodronate liposome (LC, 1.3 ml/kg/wk, i.v.) combined with a high sodium (4%) diet for 4 weeks. Western blot showed that CAP pretreatment further decreased renal TRPV1 levels after I/R (P<0.05), which was not affected by LC treatment. Macrophage infiltration in the renal cortex and medulla and renal proinflammatory cytokine (TNF-α and IL-1 β) levels were increased in I/R rats and further intensified in I/R+CAP rats (P<0.05), which were abolished by LC in both I/R and I/R+CAP groups. Mean arterial pressure (MAP) was elevated in I/R rats and further increased in I/R+CAP rats (P<0.05), which was prevented by LC in both I/R and I/R+CAP groups. Decreased creatinine clearance (Sham: 0.54±0.06, I/R: 0.28±0.02, I/R+CAP: 0.16±0.02, Sham+LC: 0.54±0.03, I/R+LC: 0.51±0.04, I/R+CAP+LC: 0.49±0.04 ml/min/100 gbwt, p<0.05) and increased levels of plasma urea, urinary 8-isoprostane, renal connective tissue growth factor (CTGF), and renal collage I and IV were observed in I/R rats and exacerbated in I/R+CAP rats (P<0.05), which were restored to normal levels by LC in both I/R and I/R+CAP groups. Thus, degeneration of TRPV1-positive nerves aggravates hypertension and renal inflammation and fibrosis induced by I/R and high salt intake, possibly via enhancing renal macrophage infiltration and function. These data suggest that activation of TRPV1 after renal injury conveys renal protection against inflammation and fibrosis via inhibiting macrophage infiltration.

Salt sensitivity in experimental thyroid disorders in rats

2011 ◽  
Vol 301 (2) ◽  
pp. E281-E287 ◽  
Author(s):  
Rocío Perez-Abud ◽  
Isabel Rodríguez-Gómez ◽  
Ana Belén Villarejo ◽  
Juan Manuel Moreno ◽  
Rosemary Wangensteen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Renal Injury ◽  
Salt Intake ◽  
Salt Sensitivity ◽  
High Salt ◽  
Thyroid Disorders ◽  
High Salt Intake ◽  
Male Wistar Rats ◽  
Experimental Thyroid ◽  
And Oxidative Stress

This study assessed salt sensitivity, analyzing the effects of an increased saline intake on hemodynamic, morphological, and oxidative stress and renal variables in experimental thyroid disorders. Six groups of male Wistar rats were used: control, hypothyroid, hyperthyroid, and the same groups treated with salt (8% via food intake). Body weight, blood pressure (BP), and heart rate (HR) were recorded weekly for 6 wk. Finally, BP and HR were recorded directly, and morphological, metabolic, plasma, and renal variables were measured. High-salt intake increased BP in thyroxine-treated rats but not in control or hypothyroid rats. High-salt intake increased cardiac mass in all groups, with a greater increase in hyperthyroid rats. Urinary isoprostanes and H2O2 were higher in hyperthyroid rats and were augmented by high-salt intake in all groups, especially in hyperthyroid rats. High-salt intake reduced plasma thyroid hormone levels in hyperthyroid rats. Proteinuria was increased in hyperthyroid rats and aggravated by high-salt intake. Urinary levels of aminopeptidases (glutamyl-, alanyl-, aspartyl-, and cystinylaminopeptidase) were increased in hyperthyroid rats. All aminopeptidases were increased by salt intake in hyperthyroid rats but not in hypothyroid rats. In summary, hyperthyroid rats have enhanced salt sensitivity, and high-salt intake produces increased BP, cardiac hypertrophy, oxidative stress, and signs of renal injury. In contrast, hypothyroid rats are resistant to salt-induced BP elevation and renal injury signs. Urinary aminopeptidases are suitable biomarkers of renal injury.

scholarly journals Chronic high salt intake induces renal inflammation and endothelial dysfunction that are reversed by statin

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Maria Cecilia Fiore ◽  
Pablo M Jimenez ◽  
David Cremonessi ◽  
Luis I Juncos ◽  
Nestor H Garcia
Keyword(s):  
Endothelial Dysfunction ◽  
Salt Intake ◽  
High Salt ◽  
Renal Inflammation ◽  
High Salt Intake

scholarly journals NOX4/H 2 O 2 /mTORC1 Pathway in Salt-Induced Hypertension and Kidney Injury

Hypertension ◽  
2020 ◽  
Vol 76 (1) ◽  
pp. 133-143 ◽  
Author(s):  
Vikash Kumar ◽  
Theresa Kurth ◽  
Nadezhda N. Zheleznova ◽  
Chun Yang ◽  
Allen W. Cowley
Keyword(s):  
Renal Injury ◽  
Immune Cell ◽  
Salt Intake ◽  
Chronic Phase ◽  
Kidney Injury ◽  
High Salt ◽  
High Salt Intake ◽  
Induced Hypertension

We have reported that a high-salt (4.0% NaCl) dietary intake activates mTORC1 and inhibition of this pathway with rapamycin blunts the chronic phase of salt-induced hypertension and renal injury in Dahl salt-sensitive (SS) rats. In SS rats, high-salt intake is known to increase the renal production of H 2 O 2 by NOX4, the most abundant NOX isoform in the kidney, and the global knockout of NOX4 blunts salt-sensitivity in these rats. Here, we explored the hypothesis that elevations of H 2 O 2 by NOX4 in high-salt fed SS rat stimulate mTORC1 for the full development of salt-induced hypertension and renal injury. Our in vitro studies found that H 2 O 2 activates mTORC1 independent of PI3K/AKT and AMPK pathways. To determine the in vivo relevance of NOX4/H 2 O 2 /mTORC1 in the salt-induced hypertension, SS- Nox4 knockout (SS Nox4 −/− ) rats were daily administrated with vehicle/rapamycin fed a high-salt diet for 21 days. Rapamycin treatment of SS Nox4−/− rats had shown no augmented effect on the salt-induced hypertension nor upon indices of renal injury. Significant reductions of renal T lymphocyte and macrophage together with inhibition of cell proliferation were observed in rapamycin treated rats suggesting a role of mTORC1 independent of NOX4 in the proliferation of immune cell. Given the direct activation of mTORC1 by H 2 O 2 and absence of any further protection from salt-induced hypertension in rapamycin-treated SS Nox4 −/− rats, we conclude that NOX4-H 2 O 2 is a major upstream activator of mTORC1 that contributes importantly to salt-induced hypertension and renal injury in the SS rat model.

Immune suppression blocks sodium-sensitive hypertension following recovery from ischemic acute renal failure

2008 ◽  
Vol 294 (4) ◽  
pp. R1234-R1239 ◽  
Author(s):  
Kimberly R. Pechman ◽  
David P. Basile ◽  
Hayley Lund ◽  
David L. Mattson
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Arterial Pressure ◽  
Creatinine Clearance ◽  
Immune Suppression ◽  
Salt Intake ◽  
Ischemia Reperfusion ◽  
High Salt ◽  
Sprague Dawley ◽  
High Salt Intake

The present study determined the effect of immune suppression with mycophenolate mofetil (MMF) on sodium-sensitive hypertension following recovery from ischemia reperfusion (I/R)-induced acute renal failure. Male Sprague-Dawley rats fed 0.4% NaCl chow were subjected to 40 min bilateral I/R or control sham surgery. After 35 days of recovery, when plasma creatinine levels had returned to normal, the rats were switched to 4.0% NaCl chow for 28 days and administered vehicle or MMF (20 mg·kg−1·day−1 ip). High-salt mean arterial pressure was significantly higher in I/R rats (144 ± 16 mmHg) compared with vehicle-treated sham rats (122 ± 2 mmHg). Treatment of I/R rats with MMF during the period of high salt intake prevented the salt-induced increase in arterial pressure (114 ± 3 mmHg). Conscious creatinine clearance was lower in I/R rats (0.27 ± 0.07 ml·min−1·100 g body wt−1) compared with vehicle-treated sham rats (0.58 ± 0.04 ml·min−1·100 g body wt−1); MMF treatment prevented the decrease in creatinine clearance in I/R rats (0.64 ± 0.07 ml·min−1·100 g body wt−1). I/R injury also significantly increased glomerular tissue damage and increased the presence of ED-1 positive (macrophages) and S100A4 positive cells (fibroblasts) in the renal interstitium. The I/R rats treated with MMF exhibited a significant reduction in infiltrating macrophages and fibroblasts and decreased histological damage. The present data indicate that infiltrating immune cells mediate or participate in the development of sodium-sensitive hypertension and renal damage in rats apparently recovered from renal I/R injury.

scholarly journals Protective Effect of Gamma Aminobutyric Acid against Aggravation of Renal Injury Caused by High Salt Intake in Cisplatin-Induced Nephrotoxicity

2022 ◽  
Vol 23 (1) ◽  
pp. 502
Author(s):  
Hyesook Lee ◽  
Seon Yeong Ji ◽  
Hyun Hwangbo ◽  
Min Yeong Kim ◽  
Da Hye Kim ◽  
...  
Keyword(s):  
Protective Effect ◽  
Renal Injury ◽  
Salt Intake ◽  
Protective Efficacy ◽  
High Salt ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Renal Hypertrophy ◽  
High Salt Intake

Gamma-aminobutyric acid (GABA) is one of the inhibitory neurotransmitters. Several studies have suggested that GABA supplements can reduce blood pressure and modulate the renal immune system in vitro and in vivo. In the present study, we investigated the effect of GABA-enriched salt as an alternative to traditional salt on aggravated renal injury by high salt intake in cisplatin-induced nephrotoxicity mice. High salt intake accelerated the increase of biomarkers, such as blood urea nitrogen and serum creatinine levels for renal injury in cisplatin-induced nephrotoxicity mice. However, oral administration of GABA-contained salt notably suppressed serum BUN and creatinine levels. The efficacy of GABA salt was superior to lacto GABA salt and postbiotics GABA salt. Furthermore, GABA-enriched salt markedly restored histological symptoms of nephrotoxicity including renal hypertrophy, tubular dilation, hemorrhage, and collagen deposition aggravated by salt over-loading in cisplatin-exposed mice. Among them, GABA salt showed a higher protective effect against cisplatin-induced renal histological changes than lacto GABA salt and postbiotics GABA salt. In addition, administration of high salt significantly enhanced expression levels of apoptosis and inflammatory mediators in cisplatin-induced nephrotoxicity mice, while GABA-enriched salt greatly down-regulated the expression of these mediators. Taken together, these results demonstrate the protective effect of GABA against damage caused by high salt intake in cisplatin-induced renal toxicity. Its mechanism may be due to the suppression of hematological and biochemical toxicity, apoptosis, and inflammation. In conclusion, although the protective efficacy of GABA salt on renal injury is different depending on the sterilization and filtration process after fermentation with L. brevis BJ20 and L. plantarum BJ21, our findings suggest that GABA-enriched salt has a beneficial effect against immoderate high salt intake-mediated kidney injury in patients with cisplatin-induced nephrotoxicity.

Abstract 383: Hypertensive and Renal Injury Responses to Angiotensin II and High Salt Intake in Mice Lacking the Gene for Interleukin-10

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Purnima Singh ◽  
Alexander Castillo ◽  
Dewan S Majid
Keyword(s):  
Angiotensin Ii ◽  
Renal Injury ◽  
Salt Intake ◽  
Gene Knockout ◽  
Interleukin 10 ◽  
Renal Tissue ◽  
Protective Role ◽  
High Salt ◽  
High Salt Intake ◽  
Tnf Α

Endogenous interleukin-10 (IL-10) exerts immune down-regulating action on the generation of tumor necrosis factor-alpha (TNF-α). The present study examined the hypothesis that IL-10 plays a protective role in hypertension and renal injury induced by angiotensin II (AngII) and high salt (HS) diet by minimizing TNF-α production. Systemic blood pressure (BP; monitored by implanted radio-telemetry), TNF-α level in plasma and in the kidney (by ELISA) as well as renal injury (glomerulosclerosis, GS by PAS staining and renal interstitial fibrosis, RIF by Trichrome staining) responses to chronic infusion of AngII (400 ng/min; osmotic minipump) for 2 wks were evaluated in wild-type (WT; n=11) and IL-10 gene knockout mice (KO; n=11) which were fed either normal (NS; 0.03% NaCl, n=5) or HS (4% NaCl; n=6) diets. On the last day of the experiment, a 24 hr urine collection was made using metabolic cages prior to sacrificing the mice for the collection of plasma and renal tissue samples. The mean baseline BP in KO was lower (104±3 vs 116±4 mmHg) than that in WT. Increase in BP in AngII+HS treated KO was lower (Δ 20±5 vs Δ 39±2 mmHg) than that in WT but similar in AngII+NS treated KO and WT (Δ 40±3 vs Δ 47±7 mmHg). In AngII+HS treated WT, TNF-α was higher in plasma (69±6 vs 34±4 pg/mL) and in renal tissue (208±15 vs 95±11 pg/mg protein) compared to values in WT treated with AngII+NS. In AngII+HS treated KO, TNF-α was lower in plasma (20±3 vs 180±44 pg/mL) and in renal tissue (205±23 vs 277±23 vs pg/mg protein) compared to values in KO treated with AngII+NS. The urinary nitrate/nitrite excretion rate was higher in AngII+NS (0.56±0.25 vs 0.08±0.01 mM/24 hr) and AngII+HS (1.23±0.12 vs 0.18±0.02 mM/24 hr) treated KO compared to the correspondingly treated WT. The eNOS protein expression was higher in KO treated with AngII+NS (~2 folds) or AngII+HS (~3 folds) compared to those in treated WT. GS (24.6±1.3 vs 13.8±2.1 %) and RIF (10.6±1.1 vs 7.8±0.5 %) changes were greater in AngII+NS treated KO than those in treated WT. However, the changes were minimal in HS treated groups. In conclusion, these data demonstrate that there exists an interaction of IL-10 and eNOS activity in the regulation of TNF-α in the kidney that provides a protective role by minimizing hypertension and renal injury induced by Ang II and HS intake.

scholarly journals High Salt Intake and Stroke: Meta-analysis of the Epidemiologic Evidence

2012 ◽  
Vol 18 (8) ◽  
pp. 691-701 ◽  
Author(s):  
Xiu-Yang Li ◽  
Xian-Lei Cai ◽  
Ping-Da Bian ◽  
Liu-Ru Hu
Keyword(s):  
Salt Intake ◽  
Meta Analysis ◽  
High Salt ◽  
Epidemiologic Evidence ◽  
High Salt Intake

scholarly journals Hippo-YAP/MCP-1 mediated tubular maladaptive repair promote inflammation in renal failed recovery after ischemic AKI

2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Zhihuang Zheng ◽  
Chuanlei Li ◽  
Guangze Shao ◽  
Jinqing Li ◽  
Kexin Xu ◽  
...  
Keyword(s):  
Chronic Inflammation ◽  
Ischemia Reperfusion ◽  
Hippo Pathway ◽  
Glucose Deprivation ◽  
Macrophage Infiltration ◽  
Renal Inflammation ◽  
Monocyte Chemoattractant Protein 1 ◽  
The Hippo Pathway

AbstractAcute kidney injury (AKI) is associated with significant morbidity and its chronic inflammation contributes to subsequent chronic kidney disease (CKD) development. Yes-associated protein (YAP), the major transcriptional coactivator of the Hippo pathway, has been shown associated with chronic inflammation, but its role and mechanism in AKI-CKD transition remain unclear. Here we aimed to investigate the role of YAP in AKI-induced chronic inflammation. Renal ischemia/reperfusion (I/R) was used to induce a mouse model of AKI-CKD transition. We used verteporfin (VP), a pharmacological inhibitor of YAP, to treat post-IRI mice for a period, and evaluated the influence of YAP inhibition on long-term outcomes of AKI. In our results, severe IRI led to maladaptive tubular repair, macrophages infiltration, and progressive fibrosis. Following AKI, the Hippo pathway was found significantly altered with YAP persistent activation. Besides, tubular YAP activation was associated with the maladaptive repair, also correlated with interstitial macrophage infiltration. Monocyte chemoattractant protein 1 (MCP-1) was found notably upregulated with YAP activation. Of note, pharmacological inhibition of YAP in vivo attenuated renal inflammation, including macrophage infiltration and MCP-1 overexpression. Consistently, in vitro oxygen-glucose deprivation and reoxygenation (OGD/R) induced YAP activation and MCP-1 overproduction whereas these could be inhibited by VP. In addition, we modulated YAP activity by RNA interference, which further confirmed YAP activation enhances MCP-1 expression. Together, we concluded tubular YAP activation with maladaptive repair exacerbates renal inflammation probably via promoting MCP-1 production, which contributes to AKI-CKD transition.

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