Effects of Imidapril and TA-606 on Rat Dilated Cardiomyopathy After Myocarditis

Kashimura, Takeshi; Hayashi, Manabu; Kodama, Makoto; Nakazawa, Makoto; Abe, Satoru; Yoshida, Tsuyoshi; Tachikawa, Hitoshi; Hanawa, Haruo; Kato, Kiminori; Watanabe, Kenichi; Aizawa, Yoshifusa

doi:10.1536/jhj.44.735

Cited by 5 publications

(2 citation statements)

References 21 publications

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“…25 We previously showed that long-term treatment with angiotensin-converting enzyme inhibitor and angiotensin receptor blocker attenuated LV remodeling via decreased LV fibrosis with the same model used in this study. 26 It has been known that ANP exerts a direct antifibrotic effect in the myocardium by inhibition of the cardiac rennin-angiotensin-aldosterone system. 6 Thus, although increased capillary density might be expected as one of the beneficial mechanisms in this study, we cannot exclude a potential contribution of direct effects of carperitide on the myocardium.…”

Section: Discussionmentioning

confidence: 99%

Long-term Carperitide Treatment Attenuates Left Ventricular Remodeling in Rats With Heart Failure After Autoimmune Myocarditis

Tanaka¹,

Ito²,

Kodama³

et al. 2009

Journal of Cardiovascular Pharmacology

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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.

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Section: Discussionmentioning

confidence: 99%

Long-term Carperitide Treatment Attenuates Left Ventricular Remodeling in Rats With Heart Failure After Autoimmune Myocarditis

Tanaka¹,

Ito²,

Kodama³

et al. 2009

Journal of Cardiovascular Pharmacology

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“…[3][4][5][6] We have been interested in proteins that correlate well with the progression of EAM-induced heart failure. In the present study, we conducted a proteomic analysis to specify and identify proteins which correlate well with the changes in cardiac function in the chronic phase of heart failure.…”

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confidence: 99%

Functional Proteomic Analysis of Experimental Autoimmune Myocarditis-Induced Chronic Heart Failure in the Rat

Sanzen

Ito

Ohta

et al. 2010

Biological & Pharmaceutical Bulletin

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Congenital or acquired problems in myocardium cause heart failure. To study congenital heart failure, we have used TO-2 hamsters.1,2) To study the acquired type, we have used experimental autoimmune myocarditis (EAM). The immunization of Lewis rats with pig cardiac myosin results in acute myocarditis-induced heart failure followed around 8 weeks late by a stable chronic phase.3) We have investigated the therapeutic effects of several drugs and conducted etiological studies in the acute and chronic phases of heart failure using the EAM model. [3][4][5][6] We have been interested in proteins that correlate well with the progression of EAM-induced heart failure. In the present study, we conducted a proteomic analysis to specify and identify proteins which correlate well with the changes in cardiac function in the chronic phase of heart failure. Although there have been several reports of proteomic analyses of heart failure, 7-11) none was on EAM-induced heart failure. Moreover, these reports compared only levels of proteins with those in normal heart, and did not examine the correlation between protein expression and cardiac function. A detailed comparison of changes in protein expression with changes in the heart function of the failing heart would provide insights into the mechanisms underlying myocardial remodeling and deterioration and may lead to the discovery of potential drug targets.In this study, we performed a detailed comparison of changes in protein expression in the EAM-induced chronic heart failure model with heart function and pathological parameters. We focused on major proteins in myocardium prefractionated into membranous (M) and soluble (S) fractions.We found several proteins, including glucose regulated protein (GRP)78 and heat shock protein (HSP)90b which showed excellent correlations between their levels and heart functions. MATERIALS AND METHODS Animals and ProceduresNine-week-old male Lewis rats (Charles River Japan Inc., Kanagawa, Japan) were used. Autoimmune myocarditis was induced as described previously.3) Ten immunized rats were used as a heart failure group (HF-group) and 10 age-matched normal Lewis rats were used as a control group (N-group). The morbidity of experimental autoimmune myocarditis was 100%. The acute phase of myocarditis-induced heart failure ceased at around 4 weeks and stable chronic heart failure developed. The rats were used at 8 weeks after immunization (HF-group). The protocol was approved by the Committee on the Guidelines for Animal Experimentation of Niigata University. All animals were treated in accordance with the guidelines for animal experiments as laid out by our institute.Measurement of Hemodynamic Parameters Echo cardiographs and hemodynamic parameters were measured under 2% isoflurane in pure oxygen gas anesthesia with spontaneous respiration.1,3) B-and M-mode echo-cardiograms were obtained using a linear scan probe (13 MHz, EUB6500, Hitachi, Tokyo, Japan). The ejection fraction (EF) and fractional shortening (FS) were calculated. Left ventricular press...

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Effects of angiotensin-II receptor blocker candesartan cilexetil in rats with dilated cardiomyopathy

Shirai

Watanabe

et al. 2005

Mol Cell Biochem

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We examined effects of an angiotensin-II receptor blockers, candesartan cilexetil, in rats with dilated cardiomyopathy after autoimmune myocarditis. Candesartan cilexetil showed angiotensin-II blocking action in a dose-dependent manner in rats with dilated cardiomyopathy. Twenty-eight days after immunization, surviving Lewis rats were divided into four groups and given candesartan cilexetil at 0.05 mg/kg, 0.5 mg/kg or 5 mg/kg per day (Group-C0.05, n = 15, Group-C0.5, n = 15 and Group-C5, n = 15, respectively) or vehicle alone (Group-V, n = 15). After oral administration for 1 month, the left ventricular end-diastolic pressure and heart weight/body weight ratio were lower in Group-C0.05 (13.3+/-1.1 mmHg and 3.7+/-0.2 g/kg, respectively), in Group-C0.5 (8.0+/-0.9 mmHg and 3.3+/-0.1 g/kg, respectively) and in Group-C5 (5.5+/-1 mmHg and 3.1+/-0.1 g/kg, respectively) than in Group-V (13.5+/-1.0 mmHg and 3.8+/-0.2 g/kg, respectively). The area of myocardial fibrosis was also lower in Group-C0.05 (25+/-3%), in Group-C0.5 (20+/-3%), and in Group-C5 (12+/-1%) than in Group-V (32+/-4%). Furthermore, expressions of transforming growth factor-beta1 and collagen-III mRNA were suppressed in Group-C0.05 (349+/-23% and 395+/-22%, respectively), Group-C0.5 (292+/-81% and 364+/-42%, respectively) and in Group-C5 (204+/-63% and 259+/-33%, respectively) compared with those in Group-V (367+/-26% and 437+/-18%, respectively). These results suggest that candesartan cilexetil can improve the function of inefficient heart.

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Effects of Imidapril and TA-606 on Rat Dilated Cardiomyopathy After Myocarditis

Cited by 5 publications

References 21 publications

Long-term Carperitide Treatment Attenuates Left Ventricular Remodeling in Rats With Heart Failure After Autoimmune Myocarditis

Long-term Carperitide Treatment Attenuates Left Ventricular Remodeling in Rats With Heart Failure After Autoimmune Myocarditis

Functional Proteomic Analysis of Experimental Autoimmune Myocarditis-Induced Chronic Heart Failure in the Rat

Effects of angiotensin-II receptor blocker candesartan cilexetil in rats with dilated cardiomyopathy

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