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

• Main Authors: Peng Hu, Xue Qi Zhao, Jing Wang, Hai Bo Kong, Bo Hu, Ling Lu, Yuan Han Qin
• Format: Article
• Language: English
• Published: Hindawi - SAGE Publishing 2014-12-01
• Series: Journal of the Renin-Angiotensin-Aldosterone System
• Online Access: https://doi.org/10.1177/1470320313507121

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.