Assuntos
Peptídeos e Proteínas de Sinalização Intercelular/química , Infarto do Miocárdio/tratamento farmacológico , Peptídeos/farmacologia , Sequência de Aminoácidos , Animais , Pressão Sanguínea/efeitos dos fármacos , Creatina Quinase Forma MB/metabolismo , Frequência Cardíaca/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , L-Lactato Desidrogenase/metabolismo , Masculino , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Peptídeos/química , Ratos , Ratos Wistar , Relação Estrutura-AtividadeRESUMO
Apelin-12 (A-12) peptide was synthesized by automated solid phase method and purified by reverse phase HPLC. Its homogeneity and structure were confirmed by HPLC, (1)H-NMR spectroscopy, and mass spectroscopy. Acute myocardial infarction was induced by 40-min occlusion of the left coronary artery with subsequent 60-min reperfusion in narcotized Wistar rats. Peptide A-12 was injected (intravenous bolus, 0.07 or 0.35 µmol/kg) to experimental animals simultaneously with the beginning of reperfusion. Injections of A-12 in these doses led to reduction of systolic BP to 67 and 85% of the initial level, respectively, which was virtually restored completely by the end of reperfusion, and to a significant reduction of the infarction focus in the myocardium (by 21 and 34% in comparison with the control, respectively). Injection of A-12 in a dose of 0.35 µmol/kg led to reduction of plasma concentrations of necrosis markers in comparison with the control by the end of reperfusion: MB-creatine kinase by 56%, lactate dehydrogenase by 30%. The results attest to vasodilatory effects of A-12 under conditions of heart reperfusion in vivo; the peptide injected after local ischemia limits the myocardial infarction size and reduces damage to cardiomyocyte membrane.