C-type natriuretic peptide, a novel antifibrotic and antihypertrophic agent, prevents cardiac remodeling after myocardial infarction

J Am Coll Cardiol. 2005 Feb 15;45(4):608-16. doi: 10.1016/j.jacc.2004.10.067.


Objectives: We assessed the hypothesis that in vivo administration of C-type natriuretic peptide (CNP) might attenuate cardiac remodeling after myocardial infarction (MI) through its antifibrotic and antihypertrophic action.

Background: Recently, we have shown that CNP has more potent antifibrotic and antihypertrophic effects than atrial natriuretic peptide (ANP) in cultured cardiac fibroblasts and cardiomyocytes.

Methods: Experimental MI was induced by coronary ligation in male Sprague-Dawley rats; CNP at 0.1 mug/kg/min (n = 34) or vehicle (n = 35) was intravenously infused by osmotic mini-pump starting four days after MI. Sham-operated rats (n = 34) served as controls. After two weeks of infusion, the effects of CNP on cardiac remodeling were evaluated by echocardiograpic, hemodynamic, histopathologic, and gene analysis.

Results: C-type natriuretic peptide markedly attenuated the left ventricular (LV) enlargement caused by MI (LV end-diastolic dimension, sham: 6.7 +/- 0.1 mm; MI+vehicle; 8.3 +/- 0.1 mm; MI+CNP: 7.7 +/- 0.1 mm, p < 0.01) without affecting arterial pressure. Moreover, there was a substantial decrease in LV end-diastolic pressure, and increases in dP/dt(max), dP/dt(min), and cardiac output in CNP-treated MI rats compared with vehicle-treated MI rats. Importantly, CNP infusion markedly attenuated an increase in morphometrical collagen volume fraction in the noninfarct region (sham: 3.1 +/- 0.2%; MI+vehicle: 5.7 +/- 0.5%; MI+CNP: 3.9 +/- 0.3%, p < 0.01). In addition, CNP significantly reduced an increase in cross-sectional area of the cardiomyocytes. These effects of CNP were accompanied by suppression of MI-induced increases in collagen I, collagen III, ANP, and beta-myosin heavy chain messenger ribonucleic acid levels in the noninfarct region.

Conclusions: These data suggest that CNP may be useful as a novel antiremodeling agent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cardiomegaly / prevention & control
  • Fibrosis
  • Male
  • Myocardial Infarction / complications*
  • Myocardial Infarction / pathology
  • Natriuretic Peptide, C-Type / pharmacology
  • Natriuretic Peptide, C-Type / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Ventricular Remodeling / drug effects*


  • Natriuretic Peptide, C-Type