Project description:The overlap of congenic regions in an earlier substitution mapping study suggested the location of two blood pressure quantitative trait loci (QTL)-containing regions in the q-terminus of rat chromosome 3, QTL1 and the more distal, QTL2. Male SS/jr rats and two congenic substrain rats S.R(D3Mco36-D3Mco46) and S.R(D3Mco36-D3Got166) were maintained on a low salt (0.4% NaCl Harlan Teklad diet TD7034) diet until 39-41 days of age. These 3 rat strains will be hereafter referred to as S, S.R(ET3x1), and S.R(ET3x2), respectively. At 39-41 days of age, half of the rats from each strain were fed a high (4% NaCl Harlan Teklad diet TD83033) salt diet and water ad libitum for 24 hours. Both congenic substrains carry SR/jr (R)-rat alleles for QTL2 on an S-rat genetic background, while S.R(ET3x2) also carries R-rat alleles for QTL1. Renal gene expression analysis was used to identify differentially expressed genes or genes with altered activity within the S.R(ET3x2) congenic region. Keywords: strain differences in response to dietary changes
2015-08-28 | GSE12424 | GEO
Project description:Dietary Salt effects on Renal Expression of Dahl SS/Jr (S) and Congenic Rats
Project description:The overlap of congenic regions in an earlier substitution mapping study suggested the location of two blood pressure quantitative trait loci (QTL)-containing regions in the q-terminus of rat chromosome 3, QTL1 and the more distal, QTL2. Male SS/jr rats and two congenic substrain rats S.R(D3Mco36-D3Mco46) and S.R(D3Mco36-D3Got166) were maintained on a low salt (0.4% NaCl Harlan Teklad diet TD7034) diet until 39-41 days of age and then fed an intermediate (2% NaCl Harlan Teklad diet TD94217) salt diet for 28 days. These 3 rat strains will be hereafter referred to as S, S.R(ET3x1), and S.R(ET3x2), respectively. Both congenic substrains carry SR/jr (R)-rat alleles for QTL2 on an S-rat genetic background, while S.R(ET3x2) also carries R-rat alleles for QTL1. Renal gene expression analysis was used to identify differentially expressed genes or genes with altered activity within the S.R(ET3x2) congenic region. Keywords: strain differences in response to dietary changes
Project description:Background. The Dahl salt-sensitive (SS) rat is an established model of salt-sensitive hypertension and renal damage. Recently, sodium-independent dietary effects were shown to be important in the development of the SS hypertensive phenotype. Compared to Dahl SS/JrHsdMcwi (SS/MCW) rats fed a purified diet (AIN-76A), grain-fed Dahl SS/JrHsdMcwiCrl rats (SS/CRL; Teklad 5L2F) were less susceptible to salt-induced hypertension and renal damage. Methods. With the known role of the immune system in hypertension, the present study characterized the immune cells infiltrating SS/MCW and SS/CRL kidneys. To further identify distinct molecular pathways between SS/MCW and SS/CRL, transcriptomic analysis was performed via RNA sequencing in T-cells isolated from the blood and kidneys of low and high salt-fed rats. Results. Following a 3-week high salt (4.0% NaCl) challenge, SS/CRL rats were protected from salt-induced hypertension (116.5±1.2 vs 141.9±14.4 mmHg) and albuminuria (21.7±3.5 vs 162.9±22.2 mg/day) compared to SS/MCW. Additionally, the absolute number of immune cells infiltrating the kidney was significantly reduced in SS/CRL. RNA-seq revealed >50% of all annotated genes in the entire transcriptome to be significantly differentially expressed in T-cells isolated from blood versus kidney. Pathway analysis of significant differentially expressed genes between SS/MCW and SS/CRL renal and circulating T-cells demonstrated salt-induced changes in genes related to inflammation in SS/MCW compared to metabolism-related pathways in SS/CRL. Conclusions. These functional and transcriptomic T-cell differences between SS/MCW and SS/CRL show that sodium-independent dietary effects may influence the immune response and infiltration of immune cells into the kidney, ultimately impacting susceptibility to salt-induced hypertension and renal damage.
Project description:Hypertension is a major global health burden, with high dietary sodium intake being a key environmental risk factor. The Dahl salt-sensitive (SS) rat is a well-established model for studying salt-sensitive hypertension and renal damage. To facilitate research into the cellular mechanisms of salt-sensitivity, we generated a single-cell RNA sequencing (scRNA-seq) dataset from the kidney and peripheral blood mononuclear cells (PBMCs) of Dahl SS rats. Male rats were fed either a high-salt (4% NaCl) or low-salt (0.4% NaCl) diet for three weeks. We profiled high-quality cells from kidney tissue and from PBMCs. This dataset captures the cellular diversity of these tissues, including immune, epithelial, and endothelial cell populations, under different dietary conditions. This resource provides a foundation for investigating how high sodium intake influences cellular composition, gene expression, and cell-cell communication at single-cell resolution. As the Dahl SS rat remains one of the most widely used models for hypertension research, this dataset offers a valuable reference for exploring cell-type-specific responses to salt and generating hypotheses for future mechanistic studies.
Project description:Serum and glucocorticoid-induced kinase 1 (SGK1) activates the epithelial sodium channel (eNaC) in tubules. We examined renal SGK1 abundance in salt-adaptation and in salt-sensitive hypertension. Sprague-Dawley and Dahl salt-sensitive rats were placed on either 8% or 0.3% NaCl diets for 10 days. Plasma aldosterone levels were approximately 2.5-fold greater on 0.3% versus 8% NaCl diets in both rat strains. Both serum and glucocorticoid-induced kinase 1 transcript and protein abundance were less (P<0.01) in Sprague-Dawley rats and greater (P<0.01) in Dahl salt-sensitive rats on 8% versus 0.3% NaCl diets. The cDNA sequences of serum and glucocorticoid-induced kinase 1 in both strains of rat were the same. The present results provide evidence that the abundance of serum and glucocorticoid-induced kinase 1 in rat kidney may play a role in salt adaptation and the pathogenesis of hypertension and suggests that aldosterone is not the primary inducer of SGK1 in the Sprague-Dawley rat. Keywords = Rattus norvegicus, Sprague Dawley, Dahl SS/Jr, kidney, NaCl diet Keywords: other
Project description:Substitution of chromosome 13 from Brown Norway BN/SsNHsd/Mcw (BN/Mcw) rats into the Dahl salt-sensitive SS/JrHsd/Mcw (SS/Mcw) rats resulted in substantial reduction of blood pressure salt sensitivity in this consomic rat strain designated SSBN13. In the present study, we attempted to identify genes associated with salt-sensitive hypertension by utilizing a custom, known-gene cDNA microarray to compare the mRNA expression profiles in the renal medulla (a tissue playing a pivotal role in long-term blood pressure regulation) of SS/Mcw and SSBN13 rats on either low-salt (0.4% NaCl) or high-salt (4% NaCl, 2 wk) diets. Keywords: Dahl S rat; blood pressure; kidney; consomic rats
Project description:Chromosome 2 introgression from normotensive Brown Norway (BN) rats into hypertensive Dahl salt-sensitive (SS) background (consomic S2B) reduced blood pressure (BP) and vascular inflammation under normal salt diet (NSD). We hypothesized that BN chromosome 2 contains anti-inflammatory genes that could reduce BP elevation and vascular inflammation in rats fed NSD and high salt diet (HSD). We used chromosome 2 fragment substitutions to map chromosome 2 portion associated with vascular inflammation changes and next generation sequencing (NGS) to profile microRNAs in thoracic descending aorta of SS and congenic rats fed NSD or HSD.
Project description:Arhgef11 is a Rho guanine nucleotide exchange factor previously implicated in kidney injury in the Dahl salt-sensitive rat (SS-WT). Through exchange of GDP for GTP, Arhgef11 regulates cytoskeletal structure, function, and cell-cell contacts through a variety of stimuli (e.g., G-protein coupled receptors, growth factors, and shear stress). We studied the SS-Arhgef11-/- rat model at 4-12 weeks of age under low and high salt (0.3% or 2% NaCl). To better understand the molecular mechanisms associated with renal protection from loss of Arhgef11, MS/MS proteomics was performed on kidney from SS-Arhgef11-/- and SS-WT at week 12 (low-salt). At week 12, 1017 genes and 363 proteins were observed. In summary, in vivo phenotyping provides strong evidence that increased Arhgef11 expression in the Dahl S rat leads to actin cytoskeleton mediated changes in cell morphology and cell function (impaired reuptake filtered protein) that promote kidney injury, hypertension, and decline in kidney function.