C-type natriuretic peptide ameliorates ischemia/reperfusion-induced acute kidney injury by inhibiting apoptosis and oxidative stress in rats

Life Sci. 2014 Nov 4;117(1):40-5. doi: 10.1016/j.lfs.2014.09.023. Epub 2014 Oct 2.


Aims: Although atrial natriuretic peptide has been shown to attenuate ischemia-reperfusion (IR)-induced kidney injury, the effect of natriuretic peptide receptor (NPR)-B activation on IR-induced acute kidney injury is not well documented. The purpose of the present study was to identify the effect of C-type natriuretic peptide (CNP), a selective activator of NPR-B, on the IR-induced acute kidney injury and its mechanisms involved.

Main methods: Unilaterally nephrectomized rats were insulted by IR in their remnant kidney, and they were randomly divided into three groups: sham, vehicle+IR, and CNP+IR groups. CNP (0.2μg/kg/min) was administered intravenously at the start of a 45-min renal ischemia for 2h. Rats were then killed 24h after I/R, and the blood and tissue samples were collected to assess renal function, histology, TUNEL assay, and Western blot analysis of kidney Bax and Bcl-2 expressions.

Key findings: The levels of blood urea nitrogen and serum creatinine were significantly increased in rats after IR compared with vehicle-treated rats. IR elevated apoptosis, Bcl-2/Bax ratio, TUNEL positivity, oxidative stress parameters, malondialdehyde concentration, and superoxide dismutase activity. IR also induced epithelial desquamation of the proximal tubules and glomerular shrinkage. CNP significantly attenuated the IR-induced increase in BUN and serum creatinine. Furthermore, CNP restored the suppressed renal cyclic guanosine 3' 5'-monophosphate levels caused by IR insult.

Significance: Study findings suggest that CNP could ameliorate IR-induced acute kidney injury through inhibition of apoptotic and oxidative stress pathways, possibly through NPR-B-cGMP signaling.

Keywords: Acute kidney injury; Apoptotic change; C-type natriuretic peptide (PubChem CID: 16179407); CNP; Oxidative stress; cGMP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / physiopathology
  • Acute Kidney Injury / prevention & control*
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Blood Urea Nitrogen
  • Blotting, Western
  • Creatinine / blood
  • Cyclic GMP / metabolism
  • In Situ Nick-End Labeling
  • Male
  • Malondialdehyde / metabolism
  • Natriuretic Peptide, C-Type / administration & dosage
  • Natriuretic Peptide, C-Type / metabolism*
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology*
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Rats
  • Rats, Wistar
  • Receptors, Atrial Natriuretic Factor / metabolism*
  • Reperfusion Injury / complications*
  • Reperfusion Injury / physiopathology
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Superoxide Dismutase / metabolism
  • bcl-2-Associated X Protein / genetics


  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • Natriuretic Peptide, C-Type
  • Malondialdehyde
  • Creatinine
  • Superoxide Dismutase
  • Receptors, Atrial Natriuretic Factor
  • atrial natriuretic factor receptor B
  • Cyclic GMP