title: Hyperaldosteronemia and activation of the epithelial sodium channel are not required for sodium retention in puromycin-induced nephrosis.
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.
authors.affiliation: CNRS/UPMC UMR 7134, Institut des Cordeliers, Paris, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Lourdel
authors.forename: Johannes
authors.initials: J
authors.lastname: Loffing
authors.forename: Guillaume
authors.initials: G
authors.lastname: Favre
authors.forename: Marc
authors.initials: M
authors.lastname: Paulais
authors.forename: Antoine
authors.initials: A
authors.lastname: Nissant
authors.forename: Panos
authors.initials: P
authors.lastname: Fakitsas
authors.forename: Christophe
authors.initials: C
authors.lastname: Créminon
authors.forename: Eric
authors.initials: E
authors.lastname: Féraille
authors.forename: François
authors.initials: F
authors.lastname: Verrey
authors.forename: Jacques
authors.initials: J
authors.lastname: Teulon
authors.forename: Alain
authors.initials: A
authors.lastname: Doucet
authors.forename: Georges
authors.initials: G
authors.lastname: Deschênes
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000502:physiology; D053503:Epithelial Sodium Channels; D005455:Fluorescent Antibody Technique; D006929:Hyperaldosteronism / Q000503:physiopathology*; D006955:Hypernatremia / Q000517:prevention & control*; D015151:Immunoblotting; D008297:Male; D009401:Nephrosis / Q000473:pathology / Q000503:physiopathology*; D011336:Probability; D011691:Puromycin; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D015222:Sodium Channels / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D028021:Sodium-Potassium-Chloride Symporters / Q000378:metabolism
chemical_list: D053503:Epithelial Sodium Channels; D015222:Sodium Channels; D017923:Sodium-Hydrogen Exchangers; D028021:Sodium-Potassium-Chloride Symporters; D011691:Puromycin