C-type Natriuretic Peptide: A Multifaceted Paracrine Regulator in the Heart and Vasculature

Int J Mol Sci. 2019 May 8;20(9):2281. doi: 10.3390/ijms20092281.


C-type natriuretic peptide (CNP) is an autocrine and paracrine mediator released by endothelial cells, cardiomyocytes and fibroblasts that regulates vital physiological functions in the cardiovascular system. These roles are conveyed via two cognate receptors, natriuretic peptide receptor B (NPR-B) and natriuretic peptide receptor C (NPR-C), which activate different signalling pathways that mediate complementary yet distinct cellular responses. Traditionally, CNP has been deemed the endothelial component of the natriuretic peptide system, while its sibling peptides, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), are considered the endocrine guardians of cardiac function and blood volume. However, accumulating evidence indicates that CNP not only modulates vascular tone and blood pressure, but also governs a wide range of cardiovascular effects including the control of inflammation, angiogenesis, smooth muscle and endothelial cell proliferation, atherosclerosis, cardiomyocyte contractility, hypertrophy, fibrosis, and cardiac electrophysiology. This review will focus on the novel physiological functions ascribed to CNP, the receptors/signalling mechanisms involved in mediating its cardioprotective effects, and the development of therapeutics targeting CNP signalling pathways in different disease pathologies.

Keywords: Natriuretic peptide; angiogenesis; cardiomyocyte; endothelial cell; fibroblast; heart failure; hypertension; inflammation; vascular.

Publication types

  • Review

MeSH terms

  • Atrial Natriuretic Factor / genetics
  • Cardiovascular System / metabolism
  • Cardiovascular System / pathology
  • Endothelial Cells / metabolism
  • Ethanolamines / metabolism*
  • Humans
  • Myocardium / metabolism*
  • Myocytes, Cardiac / metabolism
  • Natriuretic Peptide, Brain / genetics
  • Natriuretic Peptide, C-Type / genetics*
  • Natriuretic Peptide, C-Type / metabolism
  • Paracrine Communication / genetics*
  • Phenethylamines / metabolism*
  • Receptors, Atrial Natriuretic Factor / genetics


  • Ethanolamines
  • Phenethylamines
  • Natriuretic Peptide, Brain
  • Natriuretic Peptide, C-Type
  • Atrial Natriuretic Factor
  • Receptors, Atrial Natriuretic Factor
  • atrial natriuretic factor receptor B
  • atrial natriuretic factor receptor C
  • bamethan