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Hyperaldosteronemia and activation of the epithelial sodium channel are not required for sodium retention in puromycin-induced nephrosis.
- Source :
-
Journal of the American Society of Nephrology : JASN [J Am Soc Nephrol] 2005 Dec; Vol. 16 (12), pp. 3642-50. Date of Electronic Publication: 2005 Nov 02. - Publication Year :
- 2005
-
Abstract
- Edema and ascites in nephrotic syndrome mainly result from increased Na+ reabsorption along connecting tubules and cortical collecting ducts (CCD). In puromycin aminonucleoside (PAN)-induced nephrosis, increased Na+ reabsorption is associated with increased activity of the epithelial sodium channel (ENaC) and Na+,K+-ATPase, two targets of aldosterone. Because plasma aldosterone increases in PAN-nephrotic rats, the aldosterone dependence of ENaC activation in PAN nephrosis was investigated. For this purpose, (1) the mechanism of ENaC activation was compared in nephrotic and sodium-depleted rats, and (2) ENaC activity in PAN-nephrotic rats was evaluated in the absence of hyperaldosteronemia. The mechanism of ENaC activation was similar in CCD from nephrotic and sodium-depleted rats, as demonstrated by (1) increased number of active ENaC evaluated by patch clamp, (2) recruitment of ENaC to the apical membrane determined by immunohistochemistry, (3) shift in the electrophoretic profile of gamma-ENaC, and (4) increased abundance of beta-ENaC mRNA. Corticosteroid clamp fully prevented all PAN-induced changes in ENaC but did not alter the development of a full-blown nephrotic syndrome with massive albuminuria, amiloride-sensitive sodium retention, induction of CCD Na+,K+-ATPase, and ascites. It is concluded that in PAN-nephrosis, (1) ENaC activation in CCD is secondary to hyperaldosteronemia, (2) sodium retention and induction of Na+,K+-ATPase in CCD are independent of hyperaldosteronemia, and (3) ENaC is not necessarily limiting for sodium reabsorption in the distal nephron.
- Subjects :
- Animals
Biological Transport physiology
Epithelial Sodium Channels
Fluorescent Antibody Technique
Immunoblotting
Male
Nephrosis pathology
Probability
Puromycin
Rats
Rats, Sprague-Dawley
Reference Values
Reverse Transcriptase Polymerase Chain Reaction
Sensitivity and Specificity
Sodium-Hydrogen Exchangers metabolism
Sodium-Potassium-Chloride Symporters metabolism
Hyperaldosteronism physiopathology
Hypernatremia prevention & control
Nephrosis physiopathology
Sodium Channels metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1046-6673
- Volume :
- 16
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Journal of the American Society of Nephrology : JASN
- Publication Type :
- Academic Journal
- Accession number :
- 16267158
- Full Text :
- https://doi.org/10.1681/ASN.2005040363