High-salt diet upregulates activity and mRNA of renal Na(+)-K(+)-ATPase in Dahl salt-sensitive rats

1993 ◽  
Vol 264 (3) ◽  
pp. F448-F452 ◽  
Author(s):  
A. Nishi ◽  
G. Celsi ◽  
A. Aperia
Keyword(s):  
Atpase Activity ◽  
Proximal Tubule ◽  
Hormonal Regulation ◽  
High Salt ◽  
Dopa Decarboxylase ◽  
Primary Defect ◽  
High Salt Diet ◽  
Salt Diet ◽  
Tubular Cells ◽  
Proximal Tubule Segments

We examined the effect of a high-salt (HS) diet on the regulation of renal cortical Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase) in young Dahl salt-sensitive (DS) and salt-resistant (DR) rats. The activity of Na(+)-K(+)-ATPase, determined in permeabilized proximal tubule segments, was similar in DS and DR rats on normal salt (NS) diet. HS diet resulted in a twofold increase in proximal tubule Na(+)-K(+)-ATPase activity in DS rats but not in DR rats. The mRNA abundance, which was also similar in DS and DR rats on NS diet, increased after 2 days on HS diet in both innervated and denervated kidneys from DS rats but had no effect in DR rats. The activity of Na(+)-K(+)-ATPase and the content of alpha 1- and beta-protein in cortical homogenate were similar in DS and DR rats on both NS and HS diets. Treatment with benserazide, an inhibitor of dopa decarboxylase, upregulated proximal tubule Na(+)-K(+)-ATPase activity and increased Na(+)-K(+)-ATPase mRNA in DR rats on HS diet. Taken together, these data indicate that there is a primary defect in the dynamic hormonal regulation of Na(+)-K(+)-ATPase activity in intact tubular cells, which might stimulate Na(+)-K(+)-ATPase transcription.

scholarly journals Proximal tubule-targeted overexpression of the Cyp4a12-20-HETE synthase promotes salt-sensitive hypertension in male mice

2020 ◽  
Vol 319 (1) ◽  
pp. R87-R95
Author(s):  
Ankit Gilani ◽  
Kevin Agostinucci ◽  
Jonathan V. Pascale ◽  
Sakib Hossain ◽  
Sharath Kandhi ◽  
...  
Keyword(s):  
Proximal Tubule ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Fold Increase ◽  
High Salt ◽  
Kidney Cortex ◽  
Male Mice ◽  
High Salt Diet ◽  
Salt Diet ◽  
Renal Microvasculature ◽  
Salt Sensitive Hypertension

20-Hydroxyeicosatetraenoic acid (20-HETE) has been linked to blood pressure (BP) regulation via actions on the renal microvasculature and tubules. We assessed the tubular 20-HETE contribution to hypertension by generating transgenic mice overexpressing the CYP4A12-20-HETE synthase (PT-4a12 mice) under the control of the proximal tubule (PT)-specific promoter phosphoenolpyruvate carboxykinase (PEPCK). 20-HETE levels in the kidney cortex of male (967 ± 210 vs. 249 ± 69 pg/mg protein) but not female (121 ± 15 vs. 92 ± 11 pg/mg protein) PT-4a12 mice showed a 2.5-fold increase compared with wild type (WT). Renal cortical Cyp4a12 mRNA and CYP4A12 protein in male but not female PT-4a12 mice increased by two- to threefold compared with WT. Male PT-4a12 mice displayed elevated BP (142 ± 1 vs. 111 ± 4 mmHg, P < 0.0001), whereas BP in female PT-4a12 mice was not significantly different from WT (118 ± 2 vs. 117 ± 2 mmHg; P = 0.98). In male PT-4a12 mice, BP decreased when mice were transitioned from a control-salt (0.4%) to a low-salt diet (0.075%) from 135 ± 4 to 120 ± 6 mmHg ( P < 0.01) and increased to 153 ± 5 mmHg ( P < 0.05) when mice were placed on a high-salt diet (4%). Female PT-4a12 mice did not show changes in BP on either low- or high-salt diet. In conclusion, the expression of Cyp4a12 driven by the PEPCK promoter is sex specific, probably because of its X-linkage. The salt-sensitive hypertension seen in PT-4a12 male mice suggests a potential antinatriuretic activity of 20-HETE that needs to be further explored.

scholarly journals Inhibition of Na-K-ATPase in thick ascending limbs by NO depends on O2− and is diminished by a high-salt diet

2004 ◽  
Vol 287 (2) ◽  
pp. F224-F230 ◽  
Author(s):  
Marisela Varela ◽  
Marcela Herrera ◽  
Jeffrey L. Garvin
Keyword(s):  
Atpase Activity ◽  
Cultured Cells ◽  
Atp Hydrolysis ◽  
Tap Water ◽  
Normal Diet ◽  
High Salt ◽  
Thick Ascending Limb ◽  
High Salt Diet ◽  
Effect Change ◽  
Salt Diet

A high-salt diet enhances nitric oxide (NO)-induced inhibition of transport in the thick ascending limb (THAL). Long exposures to NO inhibit Na-K-ATPase in cultured cells. We hypothesized that NO inhibits THAL Na-K-ATPase after long exposures and a high-salt diet would augment this effect. Rats drank either tap water or 1% NaCl for 7–10 days. Na-K-ATPase activity was assessed by measuring ouabain-sensitive ATP hydrolysis by THAL suspensions. After 2 h, spermine NONOate (SPM; 5 μM) reduced Na-K-ATPase activity from 0.44 ± 0.03 to 0.30 ± 0.04 nmol Pi·μg protein−1·min−1 in THALs from rats on a normal diet ( P < 0.03). Nitroglycerin also reduced Na-K-ATPase activity ( P < 0.04). After 20 min, SPM had no effect (change −0.07 ± 0.05 nmol Pi·μg protein−1·min−1). When rats were fed high salt, SPM did not inhibit Na-K-ATPase after 120 min. To investigate whether ONOO− formed by NO reacting with O2− was involved, we measured O2− production. THALs from rats on normal and high salt produced 35.8 ± 0.3 and 23.7 ± 0.8 nmol O2−·min−1·mg protein−1, respectively ( P < 0.01). Because O2− production differed, we studied the effects of the O2− scavenger tempol. In the presence of 50 μM tempol, SPM did not inhibit Na-K-ATPase after 120 min (0.50 ± 0.05 vs. 0.52 ± 0.07 nmol Pi·μg protein−1·min−1). Propyl gallate, another O2− scavenger, also prevented SPM-induced inhibition of Na-K-ATPase activity. SPM inhibited pump activity in tubules from rats on high salt when O2− levels were increased with xanthine oxidase and hypoxanthine. We concluded that NO inhibits Na-K-ATPase after long exposures when rats are on a normal diet and this inhibition depends on O2−. NO donors do not inhibit Na-K-ATPase in THALs from rats on high salt due to decreased O2− production.

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.

Dopamine-dependent inhibition of jejunal Na+-K+-ATPase during high-salt diet in young but not in adult rats

1998 ◽  
Vol 275 (6) ◽  
pp. G1317-G1323 ◽  
Author(s):  
M. Augusta Vieira-Coelho ◽  
Vera A. Lucas Teixeira ◽  
Yigael Finkel ◽  
Patricio Soares-Da-Silva ◽  
Alejandro M. Bertorello
Keyword(s):  
Atpase Activity ◽  
Cellular Level ◽  
High Salt ◽  
Catecholamine Level ◽  
Adult Rats ◽  
High Salt Diet ◽  
Salt Diet ◽  
Endogenous Dopamine ◽  
Dependent Inhibition ◽  
Old Rats

During high-salt diet endogenous dopamine (DA) reduces jejunal sodium transport in young but not in adult rats. This study was designed to evaluate whether this effect is mediated, at the cellular level, by inhibition of Na+-K+-ATPase activity. Enzyme activity was determined in isolated jejunal cells by the rate of [γ-32P]ATP hydrolysis. Cells were obtained from weanling and adult rats fed either with high- or normal-salt diet. In 20-day-old but not in 40-day-old rats Na+-K+-ATPase activity was significantly reduced during high-salt diet. This inhibition was abolished by a blocker of DA synthesis. The decreased activity was associated with a decreased α1-subunit at the plasma membrane. During high-salt diet there was an increase in DA content in jejunal cells from 20-day-old rats, associated with a parallel decrease in 5-hydroxytryptamine, compared with normal-salt diet. In 40-day-old rats, however, the catecholamine level remained unchanged during high-salt diet. Incubation of isolated jejunal cells with DA resulted in a dose-dependent inhibition of Na+-K+-ATPase activity in 20- but not in 40-day-old rats. We conclude that during high-salt diet, jejunal Na+-K+-ATPase in 20-day-old rats is inhibited, and this effect is likely to be mediated by locally formed DA.

Sex Specific Adaptations to High Salt Diet Preserve Electrolyte Homeostasis with Distinct Sodium Transporter Profiles

2021 ◽  
Author(s):  
Diana L. Torres-Pinzon ◽  
Donna L. Ralph ◽  
Luciana C. Veiras ◽  
Alicia A. McDonough
Keyword(s):  
Proximal Tubule ◽  
Collecting Duct ◽  
Urine Volume ◽  
High Salt ◽  
High Salt Diet ◽  
Salt Diet ◽  
Sexual Dimorphisms ◽  
Electrolyte Homeostasis ◽  
Sodium Transporter ◽  
Excretion Rates

Kidneys continuously filter an enormous amount of sodium and adapt kidney Na+ reabsorption to match Na+ intake to maintain circulatory volume and electrolyte homeostasis. Males (M) respond to high salt (HS) diet by translocating proximal tubule Na+/H+ exchanger 3 (NHE3) to the base of the microvilli, reducing activated forms of the distal NaCl cotransporter (NCC) and epithelial Na+ channel (ENaC). Males and females (M, F) on normal salt (NS) diets present sex-specific profiles of "transporters" (co-transporters, channels, pumps and claudins) along the nephron, e.g., F exhibit 40% lower NHE3 and 200% higher NCC abundance vs. M. We tested the hypothesis that adaptations to HS diet along the nephron will, likewise, exhibit sexual dimorphisms. C57BL/6J mice were fed 15 d with 4% NaCl diet (HS) vs. 0.26% NaCl diet (NS). On HS, M and F exhibited normal plasma [Na+] and [K+], and similar urine volume, Na+, K+, and osmolal excretion rates normalized to body weight. In F, like M, HS lowered abundance of distal NCC, phosphorylated NCC, and cleaved (activated) forms of ENaC. The adaptations associated with achieving electrolyte homeostasis exhibit sex-dependent and independent mechanisms: Sex differences in baseline "transporters" abundance persist during HS diet, yet the fold changes during HS diet (normalized to NS) are similar along the distal nephron and collecting duct. Sex dependent differences observed along the proximal tubule during HS show that female kidneys adapt differently from patterns reported in males yet achieve and maintain fluid and electrolyte homeostasis.

scholarly journals Reduced lifespan of erythrocytes in Dahl/Salt sensitive rats is the cause of the renal proximal tubule damage

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Eri Manabe ◽  
Satoyasu Ito ◽  
Yoshiya Ohno ◽  
Toshiyuki Tanaka ◽  
Yoshiro Naito ◽  
...  
Keyword(s):  
Proximal Tubule ◽  
Iron Chelator ◽  
Extramedullary Hematopoiesis ◽  
Renal Proximal Tubule ◽  
High Salt ◽  
Glomerular Sclerosis ◽  
Renal Tubules ◽  
High Salt Diet ◽  
Salt Diet ◽  
Serum Haptoglobin

AbstractWe studied the mechanisms of anemia and the influence of anemia on renal pathology in Dahl/Salt Sensitive (Dahl/SS) rat, a model of cardio-renal-anemia syndrome. Erythrocyte lifespan was shortened and associated with decreased hemoglobin level in the Dahl/SS rats given high-salt diet. Serum haptoglobin decreased, reticulocytes increased, and erythropoiesis in the bone marrow and extramedullary hematopoiesis in the spleen was markedly stimulated by increased serum erythropoietin in them. As a mechanism of hemolysis, we investigated the incidence of eryptosis, suicidal death of erythrocytes. Eryptosis was increased, and red blood cell-derived microparticles, small particle which are generated in hemolytic disease, were also increased in Dahl/SS rats fed with high-salt diet. Deposition of hemosiderin and mitochondrial morphologic abnormality, a sign of ferroptosis, in proximal renal tubules was associated with intravascular hemolysis. Treatment with deferasirox, an oral iron chelator, reduced the renal proximal tubular injury and the glomerular sclerosis in Dahl/SS rats fed with high-salt diet. In conclusion, reduced half-life of erythrocytes induced by hemolysis is the major cause of anemia in Dahl/SS rat. Iron accumulation induced by hemolysis causes renal proximal tubule injury and accelerates renal damage in this model.

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

Diabetes ◽  
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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