Blunted renal dopaminergic system activity in puromycin aminonucleoside-induced nephrotic syndrome.
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 D(1)-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 D(1)-like agonist fenoldopam (10 microg/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.


CONCLUSIONS
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.
Sampaio-Maia
Benedita
B
Institute of Pharmacology and Therapeutics, Porto, Portugal.
Moreira-Rodrigues
Mónica
M
Serrão
Paula
P
Pestana
Manuel
M
D000818:Animals; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism; D004298:Dopamine / Q000096:biosynthesis*; D007668:Kidney / Q000378:metabolism*; D008297:Male; D009404:Nephrotic Syndrome / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D011692:Puromycin Aminonucleoside; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism
D011692:Puromycin Aminonucleoside; D012964:Sodium; D001142:Aromatic-L-Amino-Acid Decarboxylases; D004298:Dopamine