Paradoxical expressions of natriuretic peptide receptor-C and neutral endopeptidase account for C-type natriuretic peptide decline during the progression of experimental obstructive nephropathy

J Renin Angiotensin Aldosterone Syst. 2014 Dec;15(4):458-65. doi: 10.1177/1470320313507121. Epub 2013 Nov 4.


Introduction: C-type natriuretic peptide (CNP) selectively binds to the guanylyl cyclase coupled natriuretic peptide receptor (NPR)-B and exerts more potent antihypertrophic and antifibrotic properties. Elimination of CNP occurs mainly by neutral endopeptidase (NEP) and NPR-C.

Methods: We established a rat model of unilateral ureteral obstruction (UUO) to examine the continuous change of the CNP expression and to assess the correlations of NPR-B, NPR-C, NEP with CNP in the obstructed kidneys.

Results: The expressions of CNP mRNA and protein in the obstructed kidneys tended to be higher immediately after ligation and declined at later time points compared to sham-operated rats, measured by real-time polymerase chain reaction (PCR) and western blot analysis. Subsequent correlation analysis indicated that CNP mRNA was positively correlated with NPR-B mRNA (r=+0.673, p<0.05). In addition, the increased expression of NPR-C (r=-0.943 and -0.837 for mRNA and protein respectively, p<0.05) and NEP (r=-0.687 and -0.823 for mRNA and protein respectively, p<0.05) were accompanied by a significant decline in CNP.

Conclusions: A high level of CNP may contribute to the elevated expression of NPR-B in the early phase of UUO. More interestingly, paradoxical expressions of NPR-C and NEP may account for the decline of CNP in the obstructed kidneys.

Keywords: C-type natriuretic peptide; natriuretic peptide receptor; neutral endopeptidase; obstructive nephropathy; unilateral ureteral obstruction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Disease Progression*
  • Humans
  • Kidney Diseases / genetics
  • Kidney Diseases / metabolism*
  • Kidney Diseases / pathology*
  • Natriuretic Peptide, C-Type / chemistry
  • Natriuretic Peptide, C-Type / metabolism*
  • Neprilysin / metabolism*
  • Rats, Wistar
  • Real-Time Polymerase Chain Reaction
  • Receptors, Atrial Natriuretic Factor / metabolism*


  • Natriuretic Peptide, C-Type
  • Neprilysin
  • Receptors, Atrial Natriuretic Factor
  • atrial natriuretic factor receptor B
  • atrial natriuretic factor receptor C