Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-24596
Lourdel, S; Loffing, J; Favre, G; Paulais, M; Nissant, A; Fakitsas, P; Créminon, C; Féraille, E; Verrey, F; Teulon, J; Doucet, A; Deschênes, G (2005). Hyperaldosteronemia and activation of the epithelial sodium channel are not required for sodium retention in puromycin-induced nephrosis. Journal of the American Society of Nephrology (JASN), 16(12):3642-3650.
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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.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > Functional Genomics Center Zurich|
08 University Research Priority Programs > Systems Biology / Functional Genomics
|DDC:||570 Life sciences; biology|
610 Medicine & health
|Date:||02 November 2005|
|Deposited On:||18 Dec 2009 06:46|
|Last Modified:||23 Nov 2012 15:02|
|Publisher:||American Society of Nephrology|
|Free access at:||Publisher DOI. An embargo period may apply.|
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