Effects of adrenalectomy and chronic adrenal corticosteroid replacement on potassium transport in rat kidney.

Giebisch, Gerhard; Klein-Robbenhaar, G.; Wade, James B.; DeFronzo, Ralph A.

doi:10.1172/jci111832

Cited by 76 publications

(64 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mRNA values in these parameters in the ADX group were not statistically different from values observed in the sham-ADX group. COL-I, TGF-β1, CTGF and PAI-1 mRNA relative expression levels in CsA-treated animals had notable increases (p < 0.05, respectively), which were 34 13, respectively. Concomitant administration of Epl significantly decreased the mRNA expression of COL-I, TGF-β1 and PAI-1 (p < 0.05 vs. CsA, respectively), and though a slight decrease in CTGF expression was observed there was no significant difference as compared with the CsA group (Figure 4).…”

Section: Molecular Studiesmentioning

confidence: 95%

See 1 more Smart Citation

Inhibition of local aldosterone by eplerenone reduces renal structural damage in a novel model of chronic cyclosporine A nephrotoxicity

Sun

Rui

et al. 2014

J Renin Angiotensin Aldosterone Syst

View full text Add to dashboard Cite

Background and objective:The fact that mineralocorticoid receptor antagonists reduce structural and functional alterations induced by cyclosporine A (CsA) indicates that aldosterone plays a key role in chronic CsA nephrotoxicity. We and other researchers have reported local renal aldosterone synthesis. To investigate local renal aldosterone's role in chronic CsA nephrotoxicity, we evaluated the effect of eplerenone (Epl) on renal structural damage and renal dysfunction in adrenalectomized (ADX) rats, and assessed whether the therapeutic benefit was associated with reduction of transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF), plasminogen activator inhibitor type 1 (PAI-1) and collagen I (COL-I) expression. Methods: Male Sprague-Dawley rats fed a normal-sodium diet were divided in four groups: sham-ADX, ADX, CsA, or Epl. Rats in the ADX, CsA and Epl groups were adrenalectomized first. Aldosterone, sodium and potassium levels in serum and urine were measured on the second day. Two weeks later, vehicle (sham-ADX and ADX group), CsA (25mg/ kg/d), or CsA and Epl (100 mg/ kg/d) combination was administrated, respectively. After six weeks, urinary protein, creatinine clearance (C cr ), tubulointerstitial fibrosis (TIF), aldosterone level in kidney, and renal aldosterone synthase CYP11B2, COL-I, TGF-β1, CTGF and PAI-1 gene expression levels were determined. Results: On the second day after surgery, adrenalectomized rats showed undetectable aldosterone with natriuresis, hyponatremia, decreased urinary potassium excretion and hyperpotassemia. CsA reduced C cr , induced urinary proteins and up-regulated COL-I, TGF-β1, CTGF and PAI-1 gene expression with a significant development of TIF. Eplerenone administration prevented TIF and COL-I, TGF-β1 and PAI-1 up-regulation but did not improve renal function. Conclusion:Our results suggest local renal aldosterone is an important mediator of renal injury induced by CsA.

show abstract

Section: Molecular Studiesmentioning

confidence: 95%

“…All adrenalectomized rats were supplemented with dexamethasone (12 μg/kg/d, intraperitoneally) to maintain glomerular filtration rate and fasting plasma glucose. 34 Sham-ADX received sterile distilled water at a dose of 1 ml/kg/d intraperitoneally as vehicle.…”

Section: Surgical Proceduresmentioning

confidence: 99%

Inhibition of local aldosterone by eplerenone reduces renal structural damage in a novel model of chronic cyclosporine A nephrotoxicity

Sun

Rui

et al. 2014

J Renin Angiotensin Aldosterone Syst

View full text Add to dashboard Cite

show abstract

“…Control rats received combined treatment with osmotic minipumps that contained aldosterone plus subcutaneous injections of dexamethasone (Research Plus) dissolved in peanut oil at a dose of 12 g/kg per d starting immediately after adrenalectomy. This dose of dexametha-sone has been reported to maintain normal weight gain, GFR, and fasting plasma glucose and insulin levels in adrenalectomized rats (11). For this study, we elected to use hormone-replaced adrenalectomized rats as controls, rather than intact (unaltered) animals.…”

Section: Animal Modelmentioning

confidence: 99%

Molecular Mechanisms of Impaired Urinary Concentrating Ability in Glucocorticoid-Deficient Rats

Chen¹,

Cadnapaphornchai²,

Summer³

et al. 2005

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

The purpose of this study was to examine urinary concentrating ability and protein expression of renal aquaporins and ion transporters in glucocorticoid-deficient (GD) rats in response to water deprivation as compared with control rats. Rats underwent bilateral adrenalectomies, followed only by aldosterone replacement (GD) or both aldosterone and dexamethasone replacement (control). As compared with control rats, the GD rats demonstrated a decrease in cardiac output and mean arterial pressure. In response to 36-h water deprivation, GD rats demonstrated significantly greater urine flow rate and decreased urine osmolality as compared with control rats at comparable serum osmolality and plasma vasopressin concentrations. The initiator of the countercurrent concentrating mechanism, the sodium-potassium-2 chloride co-transporter, was significantly decreased, as was the medullary osmolality in the GD rats versus control rats. There was also a decrease in inner medulla aquaporin-2 (AQP2) and urea transporter A1 (UT-A1) in GD rats as compared with control rats. There was a decrease in outer medulla Gs␣ protein, an important factor in vasopressin-mediated regulation of AQP2. Immunohistochemistry studies confirmed the decreased expression of AQP2 and UT-A1 in kidneys of GD rats as compared with control. In summary, impairment in the urinary concentrating mechanism was documented in GD rats in association with impaired countercurrent multiplication, diminished osmotic equilibration via AQP2, and diminished urea equilibration via UT-A1. These events occurred primarily in the relatively oxygen-deficient medulla and may have been initiated, at least in part, by the decrease in mean arterial pressure and thus renal perfusion pressure in this area of the kidney.

show abstract

“…to excrete an acute infusion of potassium (25) and induces amplification of the basolateral membrane of principal cells in the initial collecting tubule (26). A chronic high potassium intake also increases Na,K-ATPase in cortical collecting tubules of adrenalectomized adrenal hormone-deficient animals (13)(14)(15).…”

Section: Introductionmentioning

confidence: 99%

Independent effects of aldosterone and potassium on induction of potassium adaptation in rat kidney.

Stanton¹,

Pan²,

Deetjen³

et al. 1987

J. Clin. Invest.

Self Cite

View full text Add to dashboard Cite

We examined the independent effects of a high potassium diet and increased aldosterone levels on the development of renal potassium adaptation. This condition is defined by the increased ability of the kidneys to excrete an acute infusion of potassium. Rats were adrenalectomized (ADX) and received aldosterone at basal levels (0.5 Asg/100 g * d) or at high levels (2.0 ;g/100 go d) for 10 d. In each experimental group, animals received either a control diet or a high potassium diet. In ADX animals with basal aldosterone levels, a high potassium intake increased but did not completely restore the ability to excrete potassium and induced proliferation of the basolateral membrane of principal cells in the collecting tubule (i.e, morphologic adaptation). In contrast, increased aldosterone did not induce functional adaptation. Elevated aldosterone and dietary potassium intake were required to produce functional potassium adaptation indistinguishable from that in potassium-loaded, adrenal-intact animals.

show abstract

Effects of adrenalectomy and chronic adrenal corticosteroid replacement on potassium transport in rat kidney.

Cited by 76 publications

References 44 publications

Inhibition of local aldosterone by eplerenone reduces renal structural damage in a novel model of chronic cyclosporine A nephrotoxicity

Inhibition of local aldosterone by eplerenone reduces renal structural damage in a novel model of chronic cyclosporine A nephrotoxicity

Molecular Mechanisms of Impaired Urinary Concentrating Ability in Glucocorticoid-Deficient Rats

Independent effects of aldosterone and potassium on induction of potassium adaptation in rat kidney.

Contact Info

Product

Resources

About