Acute effects of aldosterone on the epithelial Na channel in rat kidney

Frindt, Gustavo; Palmer, Lawrence G.

doi:10.1152/ajprenal.00585.2014

Cited by 37 publications

(40 citation statements)

References 40 publications

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“…This process is dependent on aldosterone as evinced by the finding that rats subjected to aldosterone infusion displayed increased cleaved γ‐ENaC within 3 hours after the beginning of infusion. The results suggest that aldosterone induces the rapid cleavage and apical addressing of ENaC . Moreover, the cleaved γ‐subunit is absent in kidney tubule‐specific MR knockout mice .…”

Section: Discussionmentioning

confidence: 99%

Time‐course of sodium transport along the nephron in nephrotic syndrome: The role of potassium

et al. 2019

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The mechanism of sodium retention and its location in kidney tubules may vary with time in nephrotic syndrome (NS). We studied the mechanisms of sodium retention in transgenic POD-ATTAC mice, which display an inducible podocyte-specific apoptosis. At day 2 after the induction of NS, the increased abundance of NHE3 and phosphorylated NCC in nephrotic mice compared with controls suggest that early sodium retention occurs mainly in the proximal and distal tubules. At day 3, the abundance of NHE3 normalized, phosphorylated NCC levels decreased, and cleavage and apical localization of γ-ENaC increased in nephrotic mice. These findings indicate that sodium retention shifted from the proximal and distal tubules to the collecting system. Increased cleavage and apical localization of γ-ENaC persisted at day 5 in nephrotic mice when hypovolemia resolved and steady-state was reached.Sodium retention and γ-ENaC cleavage were independent of the increased plasma levels of aldosterone. Nephrotic mice displayed decreased glomerular filtration rate and urinary potassium excretion associated with hyperkaliemia at day 3. Feeding nephrotic mice with a low potassium diet prevented hyperkaliemia, γ-ENaC cleavage, and led to persistent increased phosphorylation of NCC. These results suggest that potassium homeostasis is a major determinant of the tubular site of sodium retention in nephrotic mice. K E Y W O R D Saldosterone paradox, edema, ENaC, hyperkalemia, proteinuria, SRAA | 2409 DIZIN et al.

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Section: Discussionmentioning

confidence: 99%

Time‐course of sodium transport along the nephron in nephrotic syndrome: The role of potassium

et al. 2019

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“…Whole‐cell amiloride‐sensitive currents were measured in principal cells of isolated, split‐open cortical collecting ducts (CCDs) as described previously (Frindt & Palmer, , ).…”

Section: Methodsmentioning

confidence: 99%

“…The correlation between biochemical and functional measurements is not perfect. We recently reported that, during acute administration of aldosterone to rats, surface expression increased more rapidly than channel activity (Frindt & Palmer, ). Conversely, in mice, deletion of the gene for serum and glucocorticoid induced kinase 1 (Sgk1) suppressed increases in surface expression but not that of channel activity in response to chronic hormone treatment (Yang et al .…”

Section: Introductionmentioning

confidence: 99%

Na restriction activates epithelial Na channels in rat kidney through two mechanisms and decreases distal Na⁺ delivery

Frindt

Yang

Bamberg

et al. 2018

The Journal of Physiology

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Changes in the activity of the epithelial Na channel (ENaC) help to conserve extracellular fluid volume. In rats fed a low-salt diet, proteolytic processing of ENaC increased within 1 day, and was almost maximal after 3 days. The rapid increase in the abundance of cleaved αENaC and γENaC correlated with decreased urinary Na excretion and with increased ENaC surface expression. By contrast, ENaC activity, measured ex vivo in isolated cortical collecting ducts, increased modestly after 3 days and required 5 days to reach maximal levels. The mineralocorticoid receptor antagonist eplerenone reversed the increase in cleaved γENaC and induced natriuresis after 1 or 3 days but failed to alter either ENaC currents or Na excretion after 7 days of Na restriction. We conclude that Na depletion, through aldosterone, stimulates ENaC via independent fast and slow mechanisms. In vivo, amiloride-induced natriuresis increased after 1 day of Na depletion. By contrast, hydrochlorothiazide (HCTZ)-induced natriuresis decreased gradually over 7 days, consistent with increased ability of ENaC activity to compensate for decreased Na reabsorption in the distal convoluted tubule. Administration of amiloride and HCTZ together increased Na excretion less in Na-depleted compared to control animals, indicating decreased delivery of Na to the distal nephron when dietary Na is restricted. Measurements of creatinine and Li clearances indicated that increased Na reabsorption by the proximal tubules is responsible for the decreased delivery. Thus, Na conservation during chronic dietary salt restriction entails enhanced transport by both proximal and distal nephron segments.

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“…It is an emerging concept that serine proteases contribute to ENaC regulation by cleaving specific sites in the extracellular domains of the a-and g-subunits (6)(7)(8)(9)(10), resulting in the release of inhibitory peptides and activation of the channel (11)(12)(13). Proteolytic activation of ENaC by serine proteases as shown in native renal tissue (14) is enhanced by low-salt diet or aldosterone infusion (15) and might involve membrane-anchored prostasin (16) and/or tissue (urinary) kallikreins (17). Under pathophysiologic conditions of proteinuria, ENaC is thought to be aberrantly activated by plasmin that arises from filtered plasminogen and conversion by the tubular urokinase-type plasminogen activator (4,6).…”

Section: Introductionmentioning

confidence: 99%

Association of Plasminuria with Overhydration in Patients with CKD

Schork

Woern

Kalbacher

et al. 2016

CJASN

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Background and objectives Hypervolemia is a common feature of patients with CKD and associated with hypertension. Recent work has shown stimulation of sodium retention by urinary plasmin during nephrotic syndrome. However, it is unclear whether plasminuria plays a role in patients with stable CKD and non-nephrotic proteinuria.Design, setting, participants, & measurements In this cross-sectional study, we analyzed the fluid status of 171 patients with CKD consecutively presenting to our outpatient clinic from 2012 to 2013 using bioimpedance spectroscopy (Body Composition Monitor [BCM]; Fresenius Medical Care, Germany) and its associations to the urinary excretion of plasminogen and plasmin from a spot urine sample. Two-electrode voltage clamp measurements were performed in Xenopus laevis oocytes expressing human epithelial sodium channel to investigate whether plasmin in concentrations found in urine can activate the channel.Results Overhydration .5% and overhydration .10% of the extracellular volume were found in 29% and 17% of the patients, respectively, and overhydration was associated with edema, hypertension, higher stages of CKD, and proteinuria. Proteinuria was the strongest independent predictor for overhydration (+0.58 L/1.73 m 2 per 10-fold increase; P,0.001). Urinary excretion of plasmin(ogen) quantified by ELISA correlated strongly with proteinuria (r=0.87) and overhydration (r=0.47). Using a chromogenic substrate, active plasmin was found in 44% of patients and correlated with proteinuria and overhydration. Estimated urinary plasmin concentrations were in a range sufficient to activate epithelial sodium channel currents in vitro. In multivariable analysis, urinary excretion of plasmin(ogen) was associated with overhydration similar to proteinuria.Conclusions Hypervolemia in patients with CKD is strongly associated with proteinuria, even in the nonnephrotic range. Protein-rich urine contains high amounts of plasminogen and active plasmin, rendering plasminuria as a possible link between proteinuria and hypervolemia.

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Acute effects of aldosterone on the epithelial Na channel in rat kidney

Cited by 37 publications

References 40 publications

Time‐course of sodium transport along the nephron in nephrotic syndrome: The role of potassium

Time‐course of sodium transport along the nephron in nephrotic syndrome: The role of potassium

Na restriction activates epithelial Na channels in rat kidney through two mechanisms and decreases distal Na⁺ delivery

Association of Plasminuria with Overhydration in Patients with CKD

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Acute effects of aldosterone on the epithelial Na channel in rat kidney

Cited by 37 publications

References 40 publications

Time‐course of sodium transport along the nephron in nephrotic syndrome: The role of potassium

Time‐course of sodium transport along the nephron in nephrotic syndrome: The role of potassium

Na restriction activates epithelial Na channels in rat kidney through two mechanisms and decreases distal Na+ delivery

Association of Plasminuria with Overhydration in Patients with CKD

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Na restriction activates epithelial Na channels in rat kidney through two mechanisms and decreases distal Na⁺ delivery