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Pharmacology ; 77(1): 1-10, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16508340

RESUMO

The aim of the present study was to compare the cardioprotective properties of long-acting calcium channel antagonist pranidipine with amlodipine in rat model of heart failure induced by autoimmune myocarditis. Twenty-eight days after immunization the surviving rats were randomized for the oral administration of low-dose amlodipine (1 mg/kg/day), high-dose amlodipine (5 mg/kg/day), pranidipine (0.3 mg/kg/day) or vehicle (0.5% methylcellulose). After oral administration for 1 month, the animals underwent echocardiography and hemodynamic analysis. Histopathology, immunohistochemistry, and Western immunoblotting were carried out in the heart samples. Both pranidipine and high-dose amlodipine increased survival rate. Although the heart rate did not differ among the four groups, left ventricular end-diastolic pressure was significantly decreased and +/-dP/dt was increased in the pranidipine- and high-dose amlodipine-treated rats, but not in low-dose amlodipine-treated rats. In comparison to amlodipine treatment, pranidipine treatment significantly reduced myocyte size and central venous pressure. Furthermore, both pranidipine and high-dose amlodipine treatment significantly reduced myocardial protein levels of atrial natriuretic peptide and inducible nitric oxide synthase, whereas pranidipine only significantly decreased tumor necrosis factor-alpha, and improved sarcoplasmic reticulum Ca2+ ATPase2 protein levels. We conclude that pranidipine ameliorates the progression of left ventricular dysfunction and cardiac remodeling in rats with heart failure after autoimmune myocarditis in a lower dose when compared to amlodipine and which may be a clinically potential therapeutic agent for the treatment of heart failure.


Assuntos
Anlodipino/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Di-Hidropiridinas/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Miocardite/tratamento farmacológico , Administração Oral , Anlodipino/administração & dosagem , Animais , Fator Natriurético Atrial/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/administração & dosagem , ATPases Transportadoras de Cálcio/metabolismo , Miosinas Cardíacas , Di-Hidropiridinas/administração & dosagem , Relação Dose-Resposta a Droga , Ecocardiografia , Fibrose , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/patologia , Frequência Cardíaca/efeitos dos fármacos , Masculino , Miocardite/induzido quimicamente , Miocárdio/metabolismo , Miocárdio/patologia , Óxido Nítrico Sintase Tipo II/metabolismo , Ratos , Ratos Endogâmicos Lew , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático , Taxa de Sobrevida , Fatores de Tempo , Função Ventricular Esquerda/efeitos dos fármacos
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