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
2015-08-28 | GSE12423 | 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. 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
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: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: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 messenger RNAs (mRNAs) and non-coding RNAs (ncRNAs) in thoracic descending aorta of SS and congenic rats fed NSD or HSD.
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: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.