Dietary Salt Regulates Renal SGK1 Abundance

Farjah, Mariam; Roxas, Bryan; Geenen, David L.; Danziger, Robert S.

doi:10.1161/01.hyp.0000063885.48344.ea

Cited by 59 publications

(32 citation statements)

References 33 publications

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“…As a matter of fact, SGK1 expression is deranged in the salt sensitive Dahl rat [14]. Moreover, moderately enhanced blood pressure values are observed in individuals carrying a variant of the SGK1 gene, affecting some 3-5% of unselected Caucasians [9,43].…”

Section: Discussionmentioning

confidence: 99%

Lack of the serum and glucocorticoid-inducible kinase SGK1 attenuates the volume retention after treatment with the PPARγ agonist pioglitazone

Artunc

Sandulache

Nasir

et al. 2008

Pflugers Arch - Eur J Physiol

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PPARγ-agonists enhance insulin sensitivity and improve glucose utilization in diabetic patients. Adverse effects of PPARγ-agonists include volume retention and edema formation. Recent observations pointed to the ability of PPARγ agonists to enhance transcription of the serum and glucocorticoid-inducible kinase SGK1, a kinase that is genomically upregulated by mineralocorticoids and stimulates various renal channels and transporters including the renal epithelial Na + channel ENaC. SGK1 has been proposed to mediate the volume retention after treatment with PPARγ agonists. To test this hypothesis, food containing the PPARγ agonist pioglitazone (0.02%, i.e., approximately 25 mg/kg bw/day) was administered to gene-targeted mice lacking SGK1 (sgk1 −/− , n=12) and their wild-type littermates (sgk1 +/+ , n=12). According to in situ hybridization, quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and immunofluorescence, treatment with pioglitazone significantly increased renal SGK1 mRNA and protein expression in sgk1 +/+ mice. The treatment increased body weight significantly in both, sgk1 +/+ mice (+2.2±0.3 g) and sgk −/− mice (+1.3±0.2 g), and decreased hematocrit significantly in sgk1 +/+ mice (−6.5±1.0%) and sgk1 −/− mice (−3.1±0.6%). Both effects were significantly (p<0.05) more pronounced in sgk1 +/+ mice. According to Evans Blue

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Section: Discussionmentioning

confidence: 99%

Lack of the serum and glucocorticoid-inducible kinase SGK1 attenuates the volume retention after treatment with the PPARγ agonist pioglitazone

Artunc

Sandulache

Nasir

et al. 2008

Pflugers Arch - Eur J Physiol

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“…8 Thus, plasma aldosterone levels do not necessarily seem to reflect renal MR activity. These observations suggest that aldosterone-dependent 6,7 and/or aldosterone-independent [8][9][10][11] MR activation may have an essential role in CKD pathophysiology and that MR blockade may be an effective renoprotective strategy. Indeed, clinical studies have shown that plasma aldosterone profiles are not predictive of the antihypertensive efficacy of MR blockade.…”

Section: Renoprotective Effect Of Mr Blockadementioning

confidence: 91%

Rationale and design of the Eplerenone combination Versus conventional Agents to Lower blood pressure on Urinary Antialbuminuric Treatment Effect (EVALUATE) trial: a double-blinded randomized placebo-controlled trial to evaluate the antialbuminuric effects of an aldosterone blocker in hypertensive patients with albuminuria

et al. 2010

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on behalf of the EVALUATE Study InvestigatorsAlthough inhibitors of the renin-angiotensin system are effective as first-line antihypertensive drugs in hypertensive patients with chronic kidney disease, they cannot completely prevent the progression of renal injury. Many animal studies, including our own, and a few human studies suggest that mineralocorticoid receptor blockade could inhibit the ongoing renal damage in chronic kidney disease. Thus, we designed this double-blinded, randomized, placebo-controlled trial to evaluate the antialbuminuric effect of a low dose (50 mg day À1 ) of the mineralocorticoid receptor antagonist eplerenone. The study subjects will include 340 hypertensive patients (blood pressure: 130-180/80-100 mm Hg) with albuminuria (urinary albumin/creatinine ratio: 30-600 mg g À1 in the first morning void urine), who are treated with an inhibitor of the renin-angiotensin system. Other classes of antihypertensive drugs may be added as needed to achieve the target blood pressure (o130/80 mm Hg). The primary study end point is the change in the urinary albumin/creatinine ratio after a 1-year study period. This trial is expected to show whether a low dose of mineralocorticoid receptor antagonists can exert an antialbuminuric effect in patients with chronic kidney disease.

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“…24,25 In Dahl salt-sensitive (S) hypertensive rats, salt loading upregulates the renal expression of serum-and glucocorticoid-inducible kinase 1 (Sgk1), a downstream mediator of MRs, despite the appropriate suppression of serum aldosterone, suggesting that MRs are activated in an aldosterone-independent manner. 26,27 However, the mechanism underlying the paradoxical response of MRs to salt loading in Dahl S rats has long been elusive.…”

Section: Rac1-induced Mr Activationmentioning

confidence: 99%

Mechanism of Salt-Sensitive Hypertension

Fujita

2014

Journal of the American Society of Nephrology

109

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A central role for the kidney among the systems contributing to BP regulation and the development of hypertension has been proposed. Both the aldosterone/ mineralocorticoid receptor pathway and the renal sympathetic nervous system have important roles in the regulation of renal excretory function and BP control, but the mechanisms underlying these processes have remained unclear. However, recent studies revealed the activation of two pathways in salt-sensitive hypertension. Notably, Rac1, a member of the Rho-family of small GTP binding proteins, was identified as a novel ligand-independent modulator of mineralocorticoid receptor activity. Furthermore, these studies point to crucial roles for the Rac1-mineralocorticoid receptor-NCC/ENaC and the renal b-adrenergic stimulant-glucocorticoid receptor-WNK4-NCC pathways in certain rodent models of salt-sensitive hypertension. The nuclear mineralocorticoid and glucocorticoid receptors may contribute to impaired renal excretory function and the resulting salt-sensitive hypertension by increasing sodium reabsorption at different tubular segments. This review provides an indepth discussion of the evidence supporting these conclusions and considers the significance with regard to treating salt-sensitive hypertension and salt-induced cardiorenal injury.

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Dietary Salt Regulates Renal SGK1 Abundance

Cited by 59 publications

References 33 publications

Lack of the serum and glucocorticoid-inducible kinase SGK1 attenuates the volume retention after treatment with the PPARγ agonist pioglitazone

Lack of the serum and glucocorticoid-inducible kinase SGK1 attenuates the volume retention after treatment with the PPARγ agonist pioglitazone

Mechanism of Salt-Sensitive Hypertension

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