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NDT Advance Access published online on October 4, 2005
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfi171
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© The Author [2005]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received April 3, 2005
Accepted August 31, 2005

Original Articles

Blunted renal dopaminergic system activity in puromycin aminonucleoside-induced nephrotic syndrome

Benedita Sampaio-Maia 1, Mónica Moreira-Rodrigues 2, Paula Serrão 1, and Manuel Pestana 2*

1 Institute of Pharmacology and Therapeutics, Faculty of Medicine, 4200-319, Porto, Portugal
2 Unit of Research and Development of Nephrology, Faculty of Medicine, 4200-319, Porto, Portugal

* To whom correspondence should be addressed.
Manuel Pestana, E-mail: mvasconcelos{at}hsjoao.min-saude.pt



  Abstract

Background. A primary tubular sodium handling abnormality has been implicated in the edema formation of nephrotic syndrome. Dopamine synthesized by renal proximal tubules behaves as an endogenous natriuretic hormone by activating D1-like receptors as a paracrine/autocrine substance.

Methods. We examined the time courses of the urinary excretion of sodium, protein and dopamine in puromycin aminonucleoside (PAN)-treated and control rats. The rats were sacrificed during greatest sodium retention (day 7) as well as during negative sodium balance (day 14) for the evaluation of renal aromatic L-amino acid decarboxylase (AADC) activity, the enzyme responsible for the synthesis of renal dopamine. Also, the influence of volume expansion (VE) and the effects of the D1-like agonist fenoldopam (10 µg/kg bw/min) on natriuresis and on proximal tubular Na+,K+-ATPase activity were examined on day 7.

Results. The daily urinary excretion of dopamine was decreased in PAN-treated rats, from day 5 and beyond. This was accompanied by a marked decrease in the renal AADC activity, on days 7 and 14. During VE, the fenoldopam-induced decrease in proximal tubular Na+,K+-ATPase activity was more pronounced in PAN-treated rats than in controls. However, the urinary sodium excretion during fenoldopam infusion was markedly increased in control rats but was not altered in PAN-treated animals.

Conclusion. PAN nephrosis is associated with a blunted renal dopaminergic system activity which may contribute to enhance the proximal tubular Na+,K+-ATPase activity. However, the lack of renal dopamine appears not to be related with the overall renal sodium retention in a state of proteinuria.

Keywords: aromatic L-amino acid decarboxylase (AADC); fenoldopam; Na+,K+-ATPase; nephrotic syndrome; renal dopamine; sodium handling.
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