Expression Of Epithelial Sodium Channel (ENaC) And Its Regulatory Genes In Brain Of Dahl S And R Rats On High Salt Diet.

Aldosterone is thought to be the main hormone to stimulate the epithelial sodium channel (ENaC) in the aldosterone-sensitive distal nephron (ASDN) comprising the late distal convoluted tubule (DCT2), the connecting tubule (CNT) and the entire collecting duct (CD). There is immunohistochemical evidence for an axial gradient of ENaC expression along the ASDN with highest expression in the DCT2 and CNT. However, most of our knowledge about renal ENaC function stems from studies in the cortical collecting duct (CCD). Here we investigated ENaC function in the transition zone of DCT2/CNT or CNT/CCD microdissected from mice maintained on different sodium diets to vary plasma aldosterone levels. Single-channel recordings demonstrated amiloride-sensitive Na+ channels in DCT2/CNT with biophysical properties typical for ENaC previously described in CNT/CCD. In animals maintained on a standard salt diet, the average ENaC-mediated whole cell current (Δ Iami) was higher in DCT2/CNT than in CNT/CCD. A low salt diet increased Δ Iami in CNT/CCD but had little effect on Δ Iami in DCT2/CNT. To investigate whether aldosterone is necessary for ENaC activity in the DCT2/CNT, we used aldosterone synthase knockout (AS−/−) mice that lack aldosterone. In CNT/CCD of AS−/− mice, Δ Iami was lower than that in wild-type (WT) animals and was not stimulated by a low salt diet. In contrast, in DCT2/CNT of AS−/− mice, Δ Iami was similar to that in DCT2/CNT of WT animals both on a standard and on a low salt diet. We conclude that ENaC function in the DCT2/CNT is largely independent of aldosterone which is in contrast to its known aldosterone sensitivity in CNT/CCD.

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Salt-Sensitive Hypertension of the Renal Tubular Cell–Specific NFAT5 (Nuclear Factor of Activated T-Cells 5) Knockout Mice

Hypertension ◽

10.1161/hypertensionaha.121.17435 ◽

2021 ◽

Author(s):

Akiko Hiramatsu ◽

Yuichiro Izumi ◽

Koji Eguchi ◽

Naomi Matsuo ◽

Qinyuan Deng ◽

...

Keyword(s):

Sodium Channel ◽

Epithelial Sodium Channel ◽

Urinary Sodium Excretion ◽

High Salt ◽

Sodium Reabsorption ◽

Renal Tubular Cell ◽

Activated T Cells ◽

High Salt Diet ◽

Renal Tubular ◽

Salt Sensitive Hypertension

The kidney plays a crucial role in blood pressure (BP) regulation by controlling sodium reabsorption along the nephron. NFAT5 (nuclear factor of activated T-cells 5) is a transcription factor that is expressed in various tissues including the kidney and is activated at hypertonic conditions as observed in the renal medulla; the role for kidney NFAT5 in BP regulation, however, remains still obscure. In the present study, we generated inducible and renal tubular cell–specific NFAT5 knockout (KO) mice and characterized their phenotype. The NFAT5 KO mice exhibited high BP, hypernatremia, polyuria, and low urinary sodium excretion without significant alterations in the plasma renin activity or aldosterone concentration. The mice fed a high-salt diet further increased BP, revealing salt-sensitive hypertension. The KO mice ehibited the increased gene expression of the epithelial sodium channel. Protein expression of epithelial sodium channel in the membrane fraction was also significantly increased in KO mice than in wild-type mice. Treatment with amiloride, an epithelial sodium channel blocker, corrected high BP, hypernatremia, and decreased urinary sodium excretion in KO mice to the same levels of those in wild-type mice. Finally, the effects of high-salt diet and amiloride in KO mice were confirmed by the radiotelemetry method. In conclusion, these data indicate that renal tubular NFAT5 should play an important role in regulating sodium reabsorption through epithelial sodium channel under high-salt conditions, thereby preventing salt-dependent hypertension.

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Implantation and pregnancy outcome of rats fed with low and high salt diet

Endocrine Abstracts ◽

10.1530/endoabs.38.p361 ◽

2015 ◽

Author(s):

Iranloye Bolanle ◽

Oludare Gabriel

Keyword(s):

Pregnancy Outcome ◽

High Salt ◽

High Salt Diet ◽

Salt Diet

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463-P: Deterioration of Atherosclerosis via Dysbiosis in ApoE Null Mice Fed with High-Salt Diet

Diabetes ◽

10.2337/db20-463-p ◽

2020 ◽

Vol 69 (Supplement 1) ◽

pp. 463-P

Author(s):

TOMONORI KIMURA ◽

YOSHITAKA HASHIMOTO ◽

TAKAFUMI SENMARU ◽

EMI USHIGOME ◽

MASAHIDE HAMAGUCHI ◽

...

Keyword(s):

High Salt ◽

High Salt Diet ◽

Salt Diet

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Faculty Opinions recommendation of ET-1 increases reactive oxygen species following hypoxia and high-salt diet in the mouse glomerulus.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718876812.793503540 ◽

2015 ◽

Author(s):

Fredrik Palm

Keyword(s):

Reactive Oxygen Species ◽

Reactive Oxygen ◽

High Salt ◽

Oxygen Species ◽

High Salt Diet ◽

Salt Diet

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Metabolic Syndrome and Salt-Sensitive Hypertension in Polygenic Obese TALLYHO/JngJ Mice: Role of Na/K-ATPase Signaling

International Journal of Molecular Sciences ◽

10.3390/ijms20143495 ◽

2019 ◽

Vol 20 (14) ◽

pp. 3495 ◽

Cited By ~ 1

Author(s):

Yanling Yan ◽

Jiayan Wang ◽

Muhammad A. Chaudhry ◽

Ying Nie ◽

Shuyan Sun ◽

...

Keyword(s):

Blood Pressure ◽

Renal Function ◽

Significant Rise ◽

Protein Carbonylation ◽

High Salt ◽

Kidney Cortex ◽

High Salt Diet ◽

Salt Diet ◽

Salt Sensitive Hypertension

We have demonstrated that Na/K-ATPase acts as a receptor for reactive oxygen species (ROS), regulating renal Na+ handling and blood pressure. TALLYHO/JngJ (TH) mice are believed to mimic the state of obesity in humans with a polygenic background of type 2 diabetes. This present work is to investigate the role of Na/K-ATPase signaling in TH mice, focusing on susceptibility to hypertension due to chronic excess salt ingestion. Age-matched male TH and the control C57BL/6J (B6) mice were fed either normal diet or high salt diet (HS: 2, 4, and 8% NaCl) to construct the renal function curve. Na/K-ATPase signaling including c-Src and ERK1/2 phosphorylation, as well as protein carbonylation (a commonly used marker for enhanced ROS production), were assessed in the kidney cortex tissues by Western blot. Urinary and plasma Na+ levels were measured by flame photometry. When compared to B6 mice, TH mice developed salt-sensitive hypertension and responded to a high salt diet with a significant rise in systolic blood pressure indicative of a blunted pressure-natriuresis relationship. These findings were evidenced by a decrease in total and fractional Na+ excretion and a right-shifted renal function curve with a reduced slope. This salt-sensitive hypertension correlated with changes in the Na/K-ATPase signaling. Specifically, Na/K-ATPase signaling was not able to be stimulated by HS due to the activated baseline protein carbonylation, phosphorylation of c-Src and ERK1/2. These findings support the emerging view that Na/K-ATPase signaling contributes to metabolic disease and suggest that malfunction of the Na/K-ATPase signaling may promote the development of salt-sensitive hypertension in obesity. The increased basal level of renal Na/K-ATPase-dependent redox signaling may be responsible for the development of salt-sensitive hypertension in polygenic obese TH mice.

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