Insight into the Anti-Inflammatory Mechanism of Action of Atrial Natriuretic Peptide, a Heart Derived Peptide Hormone: Involvement of COX-2, MMPs, and NF-kB Pathways

  • Lakshmi Priya Kalaiarasu
  • Vimala Subramanian
  • Boopathi Sowndharrajan
  • Elangovan Vellaichamy


We sought to determine the in vivo anti-inflammatory activity of atrial natriuretic peptide (ANP) using 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced acute and chronic skin inflammatory mice model. ANP treatment (2 μg/kg body weight/day/i.p. for acute and 0.5 μg/kg body weight/day/i.p. for chronic inflammatory study) was started after 30 min of TPA application. The standard drug, aspirin (ASP) (20 μg/kg body weight/day/i.p.; 10 μg/kg body weight/day/i.p., respectively) was used as a positive control for the both acute and chronic study. TPA alone treated mice exhibited a marked increase in the ear length (7 ± 0.08 vs. 13 ± 0.7 mm, p < 0.001) as well as in ear weight (80 ± 1.3 vs. 130 ± 1.5 mg, p < 0.001) as compared with control mice. Upon treatment with ANP, the increased ear length and weight were reverted back to near normal level. Similarly, ANP treatment markedly suppressed the TPA-induced chronic skin inflammatory lesion (5.7 ± 0.2 vs. 0.95 ± 0.05, p < 0.001) as compared with TPA-induced mouse skin. TPA-induced alterations in the levels of serum C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), total white blood cell (TWBC), serum tumor necrosis factor-α (TNF-α), natriuretic peptide receptor-A (NPR-A), cyclooxygenase-2 (COX-2), matrix metalloproteinase-2/-9 (MMP-2/-9) and nuclear factor kappa B (NF-κB) (p < 0.01, respectively) were reverted back to near normal levels. The results of the present study clearly show the in vivo anti-inflammatory activity of ANP, which is comparable with that of a standard drug, ASP. Our results suggest that ANP elicits its anti-inflammatory activity by down-regulating the expressions of NPR-A, COX-2, MMPs and NF-κB.


Atrial natriuretic peptide TPA Acute inflammation Chronic inflammation COX-2 NF-κB MMPs 



Dr. EV wishes to thank the Indian Council of Medical Research (ICMR), and Department of Biotechnology (DBT), India for the financial support in the form of research project.

Compliance with Ethical Standards

Conflict of Interest

The authors declare no conflict of interest.


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Lakshmi Priya Kalaiarasu
    • 1
  • Vimala Subramanian
    • 1
  • Boopathi Sowndharrajan
    • 1
  • Elangovan Vellaichamy
    • 1
  1. 1.Department of BiochemistryUniversity of MadrasChennaiIndia

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