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Open Access

Cenderitide, a novel dual GC-A and GC-B receptor activator, is a potent chronic cardiorenal fibroinhibiting peptide which suppresses aldosterone and reduces proteinuria in models of ardiorenal fibrosis

  • Fernando L Martin1Email author,
  • Paul M McKie1,
  • Jeson S Sangaralingham1,
  • Tomoko Ichiki1,
  • Gerald E Harders1,
  • Horng H Chen1 and
  • John C BurnettJr1
BMC Pharmacology201111(Suppl 1):P22

https://doi.org/10.1186/1471-2210-11-S1-P22

Published: 1 August 2011

Background

Cenderitide, also known as CD-NP, is a novel Mayo engineered designer natriuretic peptide (NP), which unlike native ANP, BNP and CNP co-activates both the guanylyl (GC)-A receptor to which ANP and BNP bind and GC-B to which CNP binds. Recognizing the aldosterone suppressing actions of GC-A activation and the potent inhibition of collagen synthesis and proliferation on fibroblasts to GC-B activation we hypothesized cenderitide would be a potent anti-fibrotic therapeutic agent. Here we defined the actions of chronic cenderitide administrated subcutaneously by pump in two models of cardiorenal fibrosis which included in a model of post myocardial infarction (MI) induced cardiorenal fibrosis and also in a model of chronic kidney disease produced by uninephrectomy (UNX).

Methods

Cenderitide was administered for 2 weeks (170 ng/kg/min, Nile Therapeutics) with an osmotic pump following MI (n=10) or UNX (n=10) while the control groups received vehicle. Cardiorenal function and structure were assessed 3 to 4 weeks after MI or UNX.

Results

Cardiorenal fibrosis was markedly suppressed by cenderitide in both models of fibrosis. Specifically, following MI, collagen content was decreased in the LV (MI:5±0.6, CD-NP:3.5±0.4 %, p<0.05), and also in the renal cortex and medulla (MI:3.5±0.5, CD-NP:1.3±0.3, p=0.002 and MI:19±5 vs CD-NP:1.2±0.3 %, p=0.0006). After UNX, CD-NP suppressed LV fibrosis vs. UNX (UNX: 4.2±0.5, CD-NP:3±0.4%, p<0.05) and reduced medullary fibrosis. CD-NP reduced aldosterone in the MI group (MI:39.4±10, CDNP: 15±1 dl/ml, p=0.036) as well in the UNX group (UNX: 30.4±6, CD-NP: 12.6±1.8 ng/dL, p<0.05). Importantly, proteinuria was also significantly reduced in CD-NP (p<0.001) in both the MI and UNX group.

Conclusion

Cenderitide is a novel designer NP that acts as a potent cardiorenal fibro-inhibiting therapeutic agent. It inhibits cardiorenal fibrosis, suppresses aldosterone and reduces proteinuria in two models of cardiorenal fibrosis. These studies support chronic SQ CD-NP as an innovative anti-fibrotic therapeutic.

Authors’ Affiliations

(1)
Cardiorenal Research Laboratory, Mayo Clinic

Copyright

© Martin et al; licensee BioMed Central Ltd. 2011

This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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