Korean J Physiol Pharmacol.  2009 Feb;13(1):1-7. 10.4196/kjpp.2009.13.1.1.

Changes of Atrial Natriuretic Peptide System in Rats with Puromycin Aminonucleoside-Induced Nephrotic Syndrome

• Bae EH
• Lee JU
• Ma SK
• Kim SW

• KMID: 2285364
• DOI: http://doi.org/10.4196/kjpp.2009.13.1.1

Abstract

Sodium retention is a hallmark of nephrotic syndrome. We investigated whether sodium retention is associated with changes of natriuretic peptide system at different stages (i.e., a sodium retaining stage and a compensatory stage) of nephrotic syndrome. At day 7 after PAN (puromycin aminonucleoside) injection, the urinary excretion of sodium was decreased, along with the development of ascites and positive sodium balance. The plasma and urinary ANP (atrial natriuretic peptide) immunoreactivities were increased. ANP mRNA expression was increased in the heart and kidney, whereas that of NPR (natriuretic peptide receptor)-A and NPR-C mRNA was decreased in the kidney. The expression of NEP was decreased in the kidney. At day 14, urinary excretion of sodium did not differ from the control. The plasma ANP level and heart ANP mRNA expression returned to their control values. The expression of ANP mRNA in the kidney was increased in association with increased urinary ANP immunoreactivities. The expression of NPR-A in the kidney became normal, whereas that of NPR-C kept decreased. The expression of NEP (neutral endopeptidase) remained decreased. These findings suggest that the increased renal ANP synthesis in association with decreased metabolism via NEP and NPR-C may play a compensatory role against the development of sodium retention in nephrotic syndrome. The decreased of NPR-A expression in the kidney may contribute to the ANP resistance at day 7. The subsequent recovery of NPR-A expression may play a role in promoting sodium excretion in later stage (at day 14).

Keyword

Nephrotic syndrome; Natriuretic peptide; Puromycin aminonucleoside

MeSH Terms

Animals
Ascites
Atrial Natriuretic Factor
Heart
Kidney
Nephrotic Syndrome
Plasma
Puromycin
Puromycin Aminonucleoside
Rats
Retention (Psychology)
RNA, Messenger
Sodium
Atrial Natriuretic Factor
Puromycin
Puromycin Aminonucleoside
RNA, Messenger
Sodium

Figure

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  Fig. 1. The concentration of ANP in plasma and urine. columns show ANP concentration in control and PAN-treated rats. At day 7, the plasma and urinary concentrations of ANP were significantly increased. At day 14, urinary ANP excretion was increased in PAN rats compared with controls, while the plasma ANP level was comparable between two groups (mean±SEM, n=8 each). ∗p<0.05 vs. control.

• 

  Fig. 2. Expression of ANP mRNA in the heart and kidney. columns show real-time PCR data representing control and PAN-treated rats. At day 7, the mRNA expression of cardiac ANP was significantly increased in the PAN-induced nephrotic syndrome. At day 14, the mRNA expression of ANP was not changed. At day 7 and 14, the mRNA expression of renal ANP was significantly increased in the PAN-induced nephrotic syndrome compared with controls (mean±SEM, n=8 each). ∗p<0.05 vs. control.

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  Fig. 3. Expression of NPR-A and NPR-C mRNA in the kidney. columns show real-time PCR data representing control and PAN-treated rats. At day 7, the mRNA expression of NPR-A and NPR-C expression was decreased. At day 14, the mRNA expression of NPR-C was decreased compared with control, while the NPR-A expression was not changed (mean±SEM, n=8 each). ∗p<0.05 vs. control.

• 

  Fig. 4. (A) Immunoblotting of NEP was decreased in PAN-treated rats compared with control. (B) Immunoperoxidase microscopy of NEP labeling was associated with apical plasma membrane of the proximal tubule in control rats. Immunoperoxidase microscopy demonstrated decreased NEP immunolabeling in the proximal tubule in PAN-treated rats (mean±SEM, n=8 each). ∗p<0.05 vs. control. Magnification: ×200.

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