Original ArticleLong-term Carperitide Treatment Attenuates Left Ventricular Remodeling in Rats With Heart Failure After Autoimmune MyocarditisTanaka, Komei MD*; Ito, Masahiro MD*; Kodama, Makoto MD*; Hoyano, Makoto MD*; Kimura, Shinpei MD*; Mitsuma, Wataru MD*; Hirono, Satoru MD*; Adachi, Takeshi MD†; Watanabe, Kenichi MD‡; Nakazawa, Mikio PhD§; Aizawa, Yoshifusa MD*Author Information From the *Division of Cardiology, Niigata University School of Medical and Dental Sciences, Niigata, Japan; †First Department of Internal Medicine, National Defense Medical College, Saitama, Japan; ‡Department of Clinical Pharmacology, Niigata University of Pharmacy and Applied Life Sciences, Niigata, Japan; and §Department of Medical Technology, School of Health Sciences, Faculty of Medicine, Niigata University, Niigata, Japan. Received for publication April 20, 2009; accepted June 1, 2009. Funding source: none. The authors report no conflicts of interest. Reprints: Masahiro Ito, MD, Division of Cardiology, Niigata University School of Medical and Dental Sciences, 1-757 Asahimachi, Niigata City, Niigata, Japan 951-8510 (e-mail: [email protected]). Journal of Cardiovascular Pharmacology: September 2009 - Volume 54 - Issue 3 - p 232-239 doi: 10.1097/FJC.0b013e3181b0cf50 Buy Metrics 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. © 2009 Lippincott Williams & Wilkins, Inc.