Enhanced expression of epithelial sodium channels in the renal medulla of Dahl S rats

2011 ◽  
Vol 89 (3) ◽  
pp. 159-168 ◽  
Author(s):  
Md. Shahrier Amin ◽  
Erona Reza ◽  
Esraa El-Shahat ◽  
Hong-Wei Wang ◽  
Frédérique Tesson ◽  
...  
Keyword(s):  
Collecting Duct ◽  
Young Male ◽  
Renal Medulla ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Enhanced Expression ◽  
Mrna And Protein Expression ◽  
Medullary Collecting Duct ◽  
Apical Localization

Inner medullary collecting duct (IMCD) cells from salt-sensitive (S) Dahl rats transport twice as much Na+ as cells from salt-resistant (R) rats, possibly related to dysregulation of the renal epithelial sodium channel (ENaC). The effect of a high-salt diet on ENaC expression in the inner medulla of S versus R rats has not yet been studied. Young, male S and R rats were placed on a regular-salt (0.3%) or high-salt (8%) diet for 2 or 4 weeks. mRNA and protein expression of ENaC subunits were studied by real-time PCR and immunoblotting. Intracellular distribution of the subunits in the IMCD was evaluated by immunohistochemistry. On regular salt, the abundance of the mRNA of β and γENaC was higher in the medulla of S rats than R rats. This was associated with a greater protein abundance of 90 kDa γENaC and higher immunoreactivity for both α and γ ENaC. High salt did not affect mRNA abundance in either strain and decreased apical staining of βENaC in IMCD of R rats. In contrast, high salt did not affect the higher apical localization of αENaC and increased the apical membrane staining for β and γENaC in the IMCD of S rats. Expression of ENaC subunits is enhanced in the medulla of S vs. R rats on regular salt, and further increased on high salt. The persistent high expression of αENaC and increase in apical localization of β and γENaC may contribute to greater retention of sodium in S rats on a high-salt diet.

Abstract 376: The Expression of (pro)renin Receptor is Upregulated in the Kidney by High Salt Diet and No Inhibition

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Rong Rong ◽  
Osamu Ito ◽  
Nobuyoshi Mori ◽  
Yuma Tamura ◽  
Akihiro Sakuyama ◽  
...  
Keyword(s):  
Collecting Duct ◽  
High Salt ◽  
Kidney Cortex ◽  
Control Group ◽  
Thick Ascending Limb ◽  
High Salt Diet ◽  
Salt Diet ◽  
Protein Levels ◽  
Nephron Segments ◽  
Sd Rats

The (pro)renin receptor ((P)RR)-bound (pro)renin not only causes the generation of angiotensin II via the increased enzymatic activity, it also activates the receptor’s own intracellular signaling pathways up-regulating the expression of the profibrotic proteins. To clarify the regulation of (P)RR expression, the present study examined the effects of high salt diet and nitric oxide synthase (NOS) inhibition on the (P)RR expression in the kidney. The nephron segments were isolated from male Sprague-Dawley (SD) rats by microdissection and bulk isolation technique, and the (P)RR mRNA and protein expressions were examined by using reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis. In adiition, 5 week-old, male SD rats were randomly divided into 3 groups: a control group, a high salt diet (HS) group and a Nω-Nitro-L-arginine (L-NAME) group, and each group was treated with vehicle, high salt diet (8%, NaCl), or L-NAME (600mg/ml in drinking water), respectively. After 4 weeks, the (P)RR expression in the kidney was compared among these groups. The (P)RR mRNA was expressed in the glomerulus (Glm), the proximal convoluted and straight tubule, the cortical and medullary thick ascending limb (TAL) and collecting duct. The (P)RR protein as well as mRNA was expressed widely in the nephron segments; the preglomerular arteriole, the Glm, the proximal tubules (PT), the medullary TAL (mTAL) and inner medullary collecting duct (IMCD). Compared with the control group, the (P)RR protein levels significantly increased in the kidney cortex of both HS group and L-NAME group by 96% (p<0.01) and 506% (p<0.01) and in the inner medulla of L-NAME group by 148% (p<0.05), but did not significantly change in the outer medulla of HS group or L-NAME group. HS increased the (P)RR protein levels in the Glm and PT by 48% (p<0.05) and 39% (p<0.01), but did not affect them in other nephron segments. These results indicated that (P)RR is expressed widely in the nephron segments and that HS and NOS inhibition upregulate the (P)RR expression in the kidney, suggesting roles of (P)RR in hypertensive kidney disorder.

scholarly journals Effect of high-salt diet on mean arterial pressure, renal epithelial sodium channels and aquaporin subunits expression levels in Spontaneously Hypertensive Rats

2019 ◽  
Author(s):  
Chitra Devi Ramachandran ◽  
Khadijeh Gholami ◽  
Sau-Kuen Lam ◽  
Mohd Rais Mustafa ◽  
See-Ziau Hoe
Keyword(s):  
Protein Expression ◽  
Fluid Intake ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Spontaneously Hypertensive ◽  
Expression Levels ◽  
Protein Levels ◽  
Wky Rats ◽  
Mrna And Protein Expression

AbstractAn increase in blood pressure (BP) by a high-salt (HS) diet may involve the changes in the expression of epithelium sodium channels (ENaCs) and aquaporins (AQPs) in the kidney which affect the sodium- and water-handling mechanisms. In the present study, spontaneously hypertensive rats (SHRs) and Wistar Kyoto (WKY) rats were exposed to HS and regular-salt (RS) diets for 6 weeks and fluid intake was monitored. After 6 weeks, mean arterial pressure (MAP) and plasma hormonal activity of atrial natriuretic peptide (ANP), levels of angiotensin II (Ang II), aldosterone and arginine vasopressin (AVP) were determined. The expression of mRNA and protein levels of ENaC and AQP subunits in kidneys were quantified by real-time PCR and Western blotting. High-salt diet caused higher MAP only in SHRs and higher fluid intake in both strains of rats when compared with their respective controls on RS diet. The plasma levels of Ang II and aldosterone were low in both SHRs and WKY rats fed with HS diet. Meanwhile, plasma ANP activity was high in both strains of rats on HS diet; whilst the AVP showed vice versa effects. The renal expression of mRNA and protein levels of α- and γ-ENaCs was lowered by HS diet in both SHRs and WKY rats. Although β-ENaC mRNA and protein expression levels were depressed in SHRs but they were enhanced in WKY rats. On the other hand, AQP-1, 2 and 7 mRNA and protein expression levels were lowered in both strains of rats fed with HS diet, while that of AQP-3, 4 and 6 showed no significant changes. The suppression of mRNA and protein expression levels of ENaC and AQP subunits suggests that the HS-induced increase in the MAP of SHRs may not be due to the renal sodium and water retention solely.

scholarly journals Collecting duct NOS1 activation is necessary for increased GFR in response to high salt diet

2018 ◽  
Vol 32 (S1) ◽  
Author(s):  
John Miller Allan ◽  
David M. Pollock ◽  
Kelly A. Hydnman ◽  
Jennifer S. Pollock
Keyword(s):  
Collecting Duct ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet

scholarly journals Loss of circadian gene Bmal1 in the collecting duct lowers blood pressure in male, but not female, mice

2020 ◽  
Vol 318 (3) ◽  
pp. F710-F719 ◽  
Author(s):  
Dingguo Zhang ◽  
Chunhua Jin ◽  
Ijeoma E. Obi ◽  
Megan K. Rhoads ◽  
Reham H. Soliman ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Collecting Duct ◽  
High Salt ◽  
Dependent Manner ◽  
Type B ◽  
Circadian Gene ◽  
High Salt Diet ◽  
Salt Diet ◽  
Female Mice ◽  
Renal Inner Medulla

Kidney function follows a 24-h rhythm subject to regulation by circadian genes including the transcription factor Bmal1. A high-salt diet induces a phase shift in Bmal1 expression in the renal inner medulla that is dependent on endothelin type B (ETB) receptors. Furthermore, ETB receptor-mediated natriuresis is sex dependent. Therefore, experiments tested the hypothesis that collecting duct Bmal1 regulates blood pressure in a sex-dependent manner. We generated a mouse model that lacks Bmal1 expression in the collecting duct, where ETB receptor abundance is highest. Male, but not female, collecting duct Bmal1 knockout (CDBmal1KO) mice had significantly lower 24-h mean arterial pressure (MAP) than flox controls (105 ± 2 vs. 112 ± 3 mmHg for male mice and 106 ± 1 vs. 108 ± 1 mmHg for female mice, by telemetry). After 6 days on a high-salt (4% NaCl) diet, MAP remained significantly lower in male CDBmal1KO mice than in male flox control mice (107 ± 2 vs. 113 ± 1 mmHg), with no significant differences between genotypes in female mice (108 ± 2 vs. 109 ± 1 mmHg). ETB receptor blockade for another 6 days increased MAP similarly in both male and female CDBmal1KO and flox control mice. However, MAP remained lower in male CDBmal1KO mice than in male flox control mice (124 ± 2 vs. 130 ± 2 mmHg). No significant differences were observed between female CDBmal1KO and flox mice during ETB blockade (130 ± 2 vs. 127 ± 2 mmHg). There were no significant genotype differences in amplitude or phase of MAP in either sex. These data suggest that collecting duct Bmal1 has no role in circadian MAP but plays an important role in overall blood pressure in male, but not female, mice.

Abstract P331: Renal Medullary Infusion of BAF312, a Sphingosine-1-phosphate Receptor-1 Agonist, Attenuates Angiotensin II-induced Hypertension

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Qing Zhu ◽  
Junping Hu ◽  
Pin-Lan Li ◽  
Ningjun Li
Keyword(s):  
Collecting Duct ◽  
Renal Medulla ◽  
Ang Ii ◽  
High Salt Diet ◽  
Salt Diet ◽  
Low Salt ◽  
Induced Hypertension ◽  
Sphingosine 1 Phosphate ◽  
S1p Receptor ◽  
Cardiovascular Functions

Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid metabolite formed by phosphorylation of sphingosine and participates in the regulation of cardiovascular functions. We have recently shown that S1P increases sodium excretion in the renal medulla possibly through inhibiting epithelial sodium channel via the S1P receptor 1 (S1P1), which is mainly localized in collecting ducts with a higher expression level in the renal medulla than the cortex. The present study tested the hypothesis that infusion of an agonist to activate S1P1 in the renal medulla attenuates angiotensin (ANG) II-induced hypertension. Treatment of the mice with a high salt diet (HS, 4% NaCl) for 2 week significantly increased the levels of S1P1 in the renal medulla compared with that in low salt (LS) control by Western blot analysis, whereas this HS-induced increase in S1P1 level was blocked in mice treated with ANG II (600ng/kg/min, sc) (relative S1P1 levels: 1.0±0.19, 1.9±0.14 and 0.9 ±0.18 in LS, HS and HS+ANG II-treated mice, respectively). Infusion of a subpressor dose of ANG II (300ng/kg/min, sc) increased the mean arterial pressure (MAP) in mice with collecting duct-specific knockout of S1P1, but not in S1P1 floxed control mice (MAP: 132±4.7 vs. 96±1.1 mmHg). In contrast, infusion of BAF312, a selective agonist of S1P1, into the renal medulla attenuated the hypertension induced by a pressor dose of ANG II (600 ng/kg/min, sc) in uninephrectomized mice (MAP: 102±1.8, 161 ±7.1 and 133±3.9 in vehicle, ANG II and ANG II+BAF312-treated mice, respectively). These data suggest that inhibition of S1P1 level in the renal medulla may contribute to the pathogenesis of ANG II-induced hypertension and that stimulating the S1P1 pathway may be used as a therapeutic strategy for the treatment of hypertension.

Abstract P328: Angiotensin II Inhibits the High Salt-induced Production of Sphigosine-1-phosphate in the Renal Medulla

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Weili Wang ◽  
Junping Hu ◽  
Pin-Lan Li ◽  
Justin L Poklis ◽  
Ningjun Li
Keyword(s):  
Angiotensin Ii ◽  
Renal Medulla ◽  
High Salt ◽  
Ang Ii ◽  
Male Adult ◽  
High Salt Diet ◽  
Salt Diet ◽  
Protein Levels ◽  
Medullary Tissue ◽  
Natriuretic Effect

We have previously shown that sphigosine-1-phosphate (S1P) produces natriuretic effects via activation of S1P receptor 1 in the renal medulla and that this natriuretic effect may be through inhibition of epithelial sodium channel. The present study examined the expression of the enzymes that produce S1P in the renal medullary tissue and tested the hypothesis that angiotensin II (ANG II) reduces the expression of S1P-producing enzyme and thereby the levels of S1P in the renal medulla. Male adult C56BL/6 mice, 10-12 weeks old, were treated with a low salt diet (LS, 0.4%), high salt diet (HS, 4% NaCl) or HS + ANG II (600ng/kg/min, S.C.) for 10 days. A high salt diet increased the level of S1P, whereas ANG II significantly inhibited the HS-induced increase of S1P levels in the renal medullary tissue. The levels of S1P were 6.6 ± 0.34, 11.4 ± 1.33 and 3.5 ± 0.49 pmol/mg of tissue in LS, HS and HS + ANG II group, respectively. There were no difference in the levels of sphingosine kinase 1 (SPHK1), the enzyme that produces S1P by phosphorylating sphingosine, among the different groups of mice by Western blot analysis. However, a high salt diet increased the protein levels of acid ceramidase (ACDase), an upstream enzyme that produces sphingosine, the substrate for SPHK1. This HS-induced increase in ACDase was inhibited by ANG II. The relative protein levels of ACDase were 1.0 ± 0.07, 1.4 ± 0.07 and 0.17 ± 0.11 in LS, HS and HS + ANG II group, respectively. These results demonstrated that a high salt diet increased the levels of S1P in the renal medulla, probably by increasing the level of one of the S1P-producing enzymes ACDase, and that ANG II reduced the levels of ACDase and S1P in the renal medulla. Given the diuretic effect of S1P, ANG II-induced reduction of S1P production in the renal medulla may be a mechanism contributing to the sodium retention and hypertension associated with excessive ANG II. (Support: NIH grant HL89563)

scholarly journals ENaC activity in the cortical collecting duct of HKα1 H+,K+-ATPase knockout mice is uncoupled from Na+ intake

2017 ◽  
Vol 312 (6) ◽  
pp. F1073-F1080 ◽  
Author(s):  
Elena Mironova ◽  
I. Jeanette Lynch ◽  
Jonathan M. Berman ◽  
Michelle L Gumz ◽  
James D. Stockand ◽  
...  
Keyword(s):  
Atpase Activity ◽  
Knockout Mice ◽  
Purinergic Signaling ◽  
Collecting Duct ◽  
High Salt ◽  
Cortical Collecting Duct ◽  
High Salt Diet ◽  
Salt Diet

Modulation of the epithelial Na+ channel (ENaC) activity in the collecting duct (CD) is an important mechanism for normal Na+ homeostasis. ENaC activity is inversely related to dietary Na+ intake, in part due to inhibitory paracrine purinergic regulation. Evidence suggests that H+,K+-ATPase activity in the CD also influences Na+ excretion. We hypothesized that renal H+,K+-ATPases affect Na+ reabsorption by the CD by modulating ENaC activity. ENaC activity in HKα1 H+,K+-ATPase knockout (HKα1−/−) mice was uncoupled from Na+ intake. ENaC activity on a high-Na+ diet was greater in the HKα1−/− mice than in WT mice. Moreover, dietary Na+ content did not modulate ENaC activity in the HKα1−/− mice as it did in WT mice. Purinergic regulation of ENaC was abnormal in HKα1−/− mice. In contrast to WT mice, where urinary [ATP] was proportional to dietary Na+ intake, urinary [ATP] did not increase in response to a high-Na+ diet in the HKα1−/− mice and was significantly lower than in the WT mice. HKα1−/− mice fed a high-Na+ diet had greater Na+ retention than WT mice and had an impaired dipsogenic response. These results suggest an important role for the HKα1 subunit in the regulation of purinergic signaling in the CD. They are also consistent with HKα1-containing H+,K+-ATPases as important components for the proper regulation of Na+ balance and the dipsogenic response to a high-salt diet. Such observations suggest a previously unrecognized element in Na+ regulation in the CD.

Effect of saline infusion on kidney and collecting duct function in atrial natriuretic peptide (ANP) gene "knockout" mice

1999 ◽  
Vol 77 (6) ◽  
pp. 454-457 ◽  
Author(s):  
U Honrath ◽  
C K Chong ◽  
L G Melo ◽  
Harald Sonnenberg
Keyword(s):  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Collecting Duct ◽  
High Salt ◽  
Saline Infusion ◽  
Kidney Weight ◽  
High Salt Diet ◽  
Salt Diet ◽  
Arterial Blood ◽  
Atrial Natriuretic

Atrial natriuretic peptide (ANP) is thought to play a role in renal regulation of salt balance by reducing tubular reabsorption of sodium and chloride. Therefore, in the chronic absence of this hormone, a defect of salt excretion should be evident. We used an ANP gene deletion model to test this premise. F2 homozygous mutant mice (-/-) and their wild-type littermates (+/+) were fed an 8% NaCl diet prior to an acute infusion of isotonic saline. Arterial blood pressures, renal excretions of salt and water, as well as collecting duct transport of fluid and electrolytes were measured. Pressures were significantly higher in -/- compared with +/+ mice (139 ± 4 vs. 101 ± 2 mmHg; 1 mmHg = 133.3 Pa). There was no difference in glomerular filtration rate (-/- = 0.84 ± 0.06; +/+ = 0.81 ± 0.04 mL·min-1·g-1 kidney weight). In the collecting duct, sodium and chloride reabsorptions were significantly higher in the -/- group than in the +/+ group. As a result, natriuresis and chloruresis were relatively reduced (UNaV: -/- = 8.6 ± 1.1; +/+ = 14.0 ± 1.1; UClV: -/- = 10.1 ± 1.4; +/+ = 16.0 ± 1.1 µmol·min-1·g-1 kidney weight). We conclude that the absence of endogenous ANP activity in mice on a high-salt diet subjected to acute saline infusion causes inappropriately high reabsorption of sodium and chloride in the medullary collecting duct, resulting in a relative defect in renal excretory capacity for salt.Key words: high-salt diet; water, sodium, chloride, and potassium transport.

Chronic hypokalemia enhances expression of the H(+)-K(+)-ATPase alpha 2-subunit gene in renal medulla

1996 ◽  
Vol 271 (2) ◽  
pp. F314-F321 ◽  
Author(s):  
K. Y. Ahn ◽  
K. Y. Park ◽  
K. K. Kim ◽  
B. C. Kone
Keyword(s):  
In Situ Hybridization ◽  
Collecting Duct ◽  
Rat Kidney ◽  
Renal Medulla ◽  
Northern Analysis ◽  
Thick Ascending Limb ◽  
Subunit Gene ◽  
Enhanced Expression ◽  
Medullary Collecting Duct

Recent molecular and physiological studies suggested that at least two H(+)-K(+)-adenosinetriphosphatase (H(+)-K(+)-ATPase) isozymes are expressed in the rat kidney and that these ion pumps respond to changes in dietary potassium balance. We used Northern analysis and in situ hybridization to analyze the expression of mRNA encoding the "colonic" isoform of the H(+)-K(+)-ATPase alpha-subunit (HK alpha 2) in normal and potassium-deprived (2 wk) rats. Control rats exhibited low levels of HK alpha 2 mRNA in the cortical and medullary thick ascending limb, distal convoluted tubule, connecting segment, and the entire collecting duct. The potassium-deprived rats expressed approximately fivefold higher levels of HK alpha 2 mRNA in the outer and inner medulla compared with controls, as well as hypertrophy and increased in situ hybridization signal in the intercalated cells of the inner stripe of the outer medullary collecting duct and the proximal inner medullary collecting duct. In contrast, renal cortical expression of HK alpha 2 mRNA was low and comparable in the two groups. Our results suggest that enhanced expression of the HK alpha 2 subunit gene in the renal medulla contributes to potassium conservation during chronic hypokalemia.

scholarly journals Knockout of the circadian clock protein PER1 results in sex-dependent alterations of ET-1 production in mice in response to a high-salt diet plus mineralocorticoid treatment

2020 ◽  
Vol 98 (9) ◽  
pp. 579-586 ◽  
Author(s):  
Lauren G. Douma ◽  
G. Ryan Crislip ◽  
Kit-Yan Cheng ◽  
Dominique Barral ◽  
Sarah Masten ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Collecting Duct ◽  
High Salt ◽  
Negative Regulator ◽  
Specific Response ◽  
Cortical Collecting Duct ◽  
High Salt Diet ◽  
Salt Diet ◽  
Female Mice ◽  
Endothelin B

Previously, we showed that global knockout (KO) of the circadian clock transcription factor PER1 in male, but not female, mice fed a high-salt diet plus mineralocorticoid treatment (HS/DOCP) resulted in nondipping hypertension and decreased night/day ratio of sodium (Na) excretion. Additionally, we have shown that the endothelin-1 (ET-1) gene is targeted by both PER1 and aldosterone. We hypothesized that ET-1 would exhibit a sex-specific response to HS/DOCP treatment in PER1 KO. Here we show that male, but not female, global PER1 KO mice exhibit a decreased night/day ratio of urinary ET-1. Gene expression analysis revealed significant genotype differences in ET-1 and endothelin A receptor (ETA) expression in male, but not female, mice in response to HS/DOCP. Additionally, both wild-type and global PER1 KO male mice significantly increase endothelin B receptor (ETB) expression in response to HS/DOCP, but female mice do not. Finally, siRNA-mediated knockdown of PER1 in mouse cortical collecting duct cells (mpkCCDc14) resulted in increased ET-1 mRNA expression and peptide secretion in response to aldosterone treatment. These data suggest that PER1 is a negative regulator of ET-1 expression in response to HS/DOCP, revealing a novel mechanism for the regulation of renal Na handling in response to HS/DOCP treatment.

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