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This Article Full Text Full Text (PDF) All Versions of this Article: 291/1/F208    most recent 00399.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by de Seigneux, S. Articles by Nielsen, S. Search for Related Content PubMed PubMed Citation Articles by de Seigneux, S. Articles by Nielsen, S.

Increased expression but not targeting of ENaC in adrenalectomized rats with PAN-induced nephrotic syndrome

¹The Water and Salt Research Center and ²Institute of Anatomy, University of Aarhus, Aarhus C; ³Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea; and ⁴Institute of Clinical Medicine, Aarhus University Hospital, Aarhus N, Denmark

Submitted 7 October 2005 ; accepted in final form 4 January 2006

Sodium retention is a hallmark of nephrotic syndrome (NS). Puromycin aminonucleoside (PAN)-induced NS is associated with high aldosterone levels and increased ENaC expression and apical targeting. However, the mechanisms associated with increased apical targeting of ENaC in NS remain undefined, and it is unclear whether this is secondary to high aldosterone levels and whether aldosterone and/or apical ENaC targeting are important for the development of sodium retention. This study aimed at uncovering 1) whether aldosterone is essential for sodium retention in PAN-induced NS, 2) whether ENaC expression or apical targeting is secondary to high aldosterone levels, and 3) the role of aldosterone in the dysregulation of sodium transporters in NS. Puromycin treatment of adrenalectomized (ADX) rats supplemented with dexamethasone induced sodium retention despite the absence of aldosterone. Immunocytochemical analyses revealed an absence of enhanced apical targeting of ENaC subunits in PAN-treated ADX (ADX-PAN) rats, with distribution of labeling similar to adrenalectomized dexamethasone-treated control rats (ADX). Moreover, ENaC subunit abundance was increased in ADX-PAN rats. The abundance of aquaporin-2 was unchanged, whereas apical targeting was enhanced. Key sodium transporters were downregulated as previously observed in nonadrenalectomized puromycin-treated rats (Kim SW, Wang W, Nielsen J, Praetorius J, Kwon TH, Knepper MA, Frøkiær J, and Nielsen S. Am J Physiol Renal Physiol 286: F922–F935, 2004), whereas the global expression of the ₁-subunit of the Na-K-ATPase was unchanged. In conclusion, PAN treatment in the absence of aldosterone induced sodium retention, increased ENaC expression, but did not change the subcellular distribution of ENaC. This indicates that the previously observed enhanced apical targeting of ENaC in PAN-induced NS (Kim SW, Wang W, Nielsen J, Praetorius J, Kwon TH, Knepper MA, Frøkiær J, and Nielsen S. Am J Physiol Renal Physiol 286: F922–F935, 2004) is caused by aldosterone and that development of sodium retention can occur in the absence of aldosterone in NS.

epithelial sodium channel; sodium retention; aldosterone; AQP2; vasopressin

This article has been cited by other articles:

				S. de Seigneux, J. Nielsen, E. T. B. Olesen, H. Dimke, T.-H. Kwon, J. Frokiaer, and S. Nielsen Long-term aldosterone treatment induces decreased apical but increased basolateral expression of AQP2 in CCD of rat kidney Am J Physiol Renal Physiol, July 1, 2007; 293(1): F87 - F99. [Abstract] [Full Text] [PDF]