Reduced activity of 11<i>β</i>‐hydroxysteroid dehydrogenase type 2 is not responsible for sodium retention in nephrotic rats

Bistrup, Claus; Thiesson, Helle C.; Jensen, Boye L.; Skøtt, Ole

doi:10.1111/j.1365-201x.2005.01428.x

Cited by 18 publications

(21 citation statements)

References 29 publications

(34 reference statements)

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“…38 To evaluate the impact of the renin-angiotensin-aldosterone system on sodium balance, we treated PAN rats with subcutaneous injections once daily of antagonists to both angiotensin II receptor and aldosterone receptor, candesartan approximately 1 mg/kg 39,40 and canrenoate approximately 100 mg/kg, 41,42 or vehicle. To compare ENaC activity in vivo, we treated control and PAN rats with a blocker of ENaC, amiloride, once daily subcutaneously.…”

Section: Experimental Protocolmentioning

confidence: 99%

“…38 Daily sodium balance was calculated as intake minus fecal and urinary output. The magnitude of accumulated sodium balance was calculated as area under the curve from days 0 through 8.…”

Section: Food Urine and Fecal Analysismentioning

confidence: 99%

“…Plasma renin, aldosterone, and AVP concentrations were determined as described previously. 38,43,44 Purification of ENaC-Activating Proteins Aprotinin (USB, Cleveland, OH) was coupled to CNBr-activated Sepharose 4B (Amersham Bioscience, Hillerod, Denmark) according to the manufacturer's protocol and added to the nephrotic urine. The beads were pelleted and washed thoroughly.…”

Section: Blood Analysismentioning

confidence: 99%

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Plasmin in Nephrotic Urine Activates the Epithelial Sodium Channel

Svenningsen

Bistrup²,

Friis³

et al. 2009

Journal of the American Society of Nephrology

227

366

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Proteinuria and increased renal reabsorption of NaCl characterize the nephrotic syndrome. Here, we show that protein-rich urine from nephrotic rats and from patients with nephrotic syndrome activate the epithelial sodium channel (ENaC) in cultured M-1 mouse collecting duct cells and in Xenopus laevis oocytes heterologously expressing ENaC. The activation depended on urinary serine protease activity. We identified plasmin as a urinary serine protease by matrix-assisted laser desorption/ ionization time of-flight mass spectrometry. Purified plasmin activated ENaC currents, and inhibitors of plasmin abolished urinary protease activity and the ability to activate ENaC. In nephrotic syndrome, tubular urokinase-type plasminogen activator likely converts filtered plasminogen to plasmin. Consistent with this, the combined application of urokinase-type plasminogen activator and plasminogen stimulated amiloride-sensitive transepithelial sodium transport in M-1 cells and increased amiloride-sensitive whole-cell currents in Xenopus laevis oocytes heterologously expressing ENaC. Activation of ENaC by plasmin involved cleavage and release of an inhibitory peptide from the ENaC ␥ subunit ectodomain. These data suggest that a defective glomerular filtration barrier allows passage of proteolytic enzymes that have the ability to activate ENaC.

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Section: Experimental Protocolmentioning

confidence: 99%

“…38 Daily sodium balance was calculated as intake minus fecal and urinary output. The magnitude of accumulated sodium balance was calculated as area under the curve from days 0 through 8.…”

Section: Food Urine and Fecal Analysismentioning

confidence: 99%

Section: Blood Analysismentioning

confidence: 99%

See 1 more Smart Citation

Plasmin in Nephrotic Urine Activates the Epithelial Sodium Channel

Svenningsen

Bistrup²,

Friis³

et al. 2009

Journal of the American Society of Nephrology

227

366

View full text Add to dashboard Cite

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“…SGK1 is expressed in the aldosterone-sensitive distal nephron (33) and stimulates the ENaC (7,9,12,16,22,26,32,33,35,41), the renal outer medullary K ϩ channel ROMK (52), and the Na ϩ -K ϩ -ATPase (40,44,53). As a matter of fact, nephrotic syndrome has previously been shown by some (8,34) but not all (51) experimentators to upregulate SGK1 protein and mRNA expression. Even if SGK1 transcript levels remained constant, SGK1-dependent stimulation of ENaC could still play a permissive role in fluid retention.…”

mentioning

confidence: 99%

“…Nephrotic syndrome can be induced by treatment with adriamycin (doxorubicin) (6,8,14,27,34,51). Due to the absence of immune-mediated injury and the lack of immune deposits, doxorubicin-induced nephrotic syndrome resembles human minimal change disease and focal segmental glomerulosclerosis (FSGS) (6).…”

mentioning

confidence: 99%

Serum- and glucocorticoid-inducible kinase 1 in doxorubicin-induced nephrotic syndrome

Artunc

Nasir²,

Amann³

et al. 2008

American Journal of Physiology-Renal Physiology

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Doxorubicin-induced nephropathy leads to epithelial sodium channel (ENaC)-dependent volume retention and renal fibrosis. The aldosterone-sensitive serum- and glucocorticoid-inducible kinase SGK1 has been shown to participate in the stimulation of ENaC and to mediate renal fibrosis following mineralocorticoid and salt excess. The present study was performed to elucidate the role of SGK1 in the volume retention and fibrosis during nephrotic syndrome. To this end, doxorubicin (15 μg/g body wt) was injected intravenously into gene-targeted mice lacking SGK1 ( sgk1 −/−) and their wild-type littermates ( sgk1 +/+). Doxorubicin treatment resulted in heavy proteinuria (>100 mg protein/mg crea) in 15/44 of sgk1 +/+ and 15/44 of sgk1 −/− mice leading to severe nephrotic syndrome with ascites, lipidemia, and hypoalbuminemia in both genotypes. Plasma aldosterone levels increased in nephrotic mice of both genotypes and was followed by increased SGK1 protein expression in sgk1 +/+ mice. Urinary sodium excretion reached signficantly lower values in sgk1 +/+ mice (15 ± 5 μmol/mg crea) than in sgk1 −/− mice (35 ± 5 μmol/mg crea) and was associated with a significantly higher body weight gain in sgk1 +/+ compared with sgk1 −/− mice (+6.6 ± 0.7 vs. +4.1 ± 0.8 g). During the course of nephrotic syndrome, serum urea concentrations increased significantly faster in sgk1 −/− mice than in sgk1 +/+ mice leading to uremia and a reduced median survival in sgk1 −/− mice (29 vs. 40 days in sgk1 +/+ mice). In conclusion, gene-targeted mice lacking SGK1 showed blunted volume retention, yet were not protected against renal fibrosis during experimental nephrotic syndrome.

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Fluvastatin inhibits the expression of fibronectin in human peritoneal mesothelial cells induced by high-glucose peritoneal dialysis solution via SGK1 pathway

Zhang

Liu

et al. 2014

Clin Exp Nephrol

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Reduced activity of 11β‐hydroxysteroid dehydrogenase type 2 is not responsible for sodium retention in nephrotic rats

Abstract: Our results do not support the hypothesis that stimulation of the MR by endogenous glucocorticoids induces sodium and fluid retention in experimental nephrotic syndrome in rats.

Cited by 18 publications

References 29 publications

Plasmin in Nephrotic Urine Activates the Epithelial Sodium Channel

Plasmin in Nephrotic Urine Activates the Epithelial Sodium Channel

Serum- and glucocorticoid-inducible kinase 1 in doxorubicin-induced nephrotic syndrome

Fluvastatin inhibits the expression of fibronectin in human peritoneal mesothelial cells induced by high-glucose peritoneal dialysis solution via SGK1 pathway

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