Long-term carperitide treatment attenuates left ventricular remodeling in rats with heart failure after autoimmune myocarditis.

Abstract

The effect of carperitide, recombinant human atrial natriuretic peptide, on chronic heart failure (HF) has not been clarified. We investigated the beneficial effects of chronic carperitide treatment in rats with HF after experimental autoimmune myocarditis. A 28-day infusion of carperitide (n = 14) or vehicle (n = 14) was administrated to the rats 4 weeks after experimental autoimmune myocarditis induction. After 4 weeks, the myocardial levels of cyclic guanosine monophosphate (cGMP), left ventricular function, myocyte hypertrophy, interstitial fibrosis, myocardial capillary vessel density, and activity of one prominent substrate of cGMP, vasodilator-stimulated phosphoprotein (VASP) that may enhance angiogenesis, were measured. Carperitide treatment increased the myocardial levels of cGMP and attenuated the functional severity along with a decreased myocyte cross-sectional area, interstitial fibrosis, and an increased capillary to myocyte ratio. Furthermore, carperitide treatment enhanced the phosphorylation of VASP at Ser239, which was preferentially phosphorylated by cGMP-dependent protein kinase but not Ser157, which was preferentially phosphorylated by cyclic adenosine monophosphate-dependent protein kinase. Long-term carperitide treatment attenuates ventricular remodeling and ameliorates the progression of chronic HF. The effects of carperitide treatment are associated with increased neovascularization among the residual myocytes and an increase of VASP activation.

• Authors: Komei Tanaka, Masahiro Ito, Makoto Kodama, Makoto Hoyano, Shinpei Kimura, Wataru Mitsuma, Satoru Hirono, Takeshi Adachi, Kenichi Watanabe, Mikio Nakazawa, Yoshifusa Aizawa
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 54 Issue 3 Pg. 232-9 (Sep 2009) ISSN: 1533-4023 [Electronic] United States
• PMID: 19668089 (Publication Type: Journal Article)

Chemical References

• Cell Adhesion Molecules
• Microfilament Proteins
• NPPA protein, human
• Phosphoproteins
• Recombinant Proteins
• vasodilator-stimulated phosphoprotein
• Atrial Natriuretic Factor
• Cyclic GMP

Topics

• Animals
• Atrial Natriuretic Factor (therapeutic use)
• Autoimmune Diseases (physiopathology)
• Capillaries (drug effects, pathology)
• Cell Adhesion Molecules (metabolism)
• Cell Size (drug effects)
• Coronary Vessels (drug effects, pathology)
• Cyclic GMP (metabolism)
• Fibrosis
• Heart Failure (drug therapy, pathology, physiopathology)
• Male
• Microfilament Proteins (metabolism)
• Myocarditis (physiopathology)
• Myocardium (metabolism, pathology)
• Neovascularization, Physiologic (drug effects)
• Phosphoproteins (metabolism)
• Phosphorylation (drug effects)
• Random Allocation
• Rats
• Rats, Inbred Lew
• Recombinant Proteins (therapeutic use)
• Stroke Volume (drug effects)
• Ventricular Function, Left (drug effects)
• Ventricular Remodeling (drug effects)