RESUMO
The cardioprotective effects of quinapril, an angiotensin-converting enzyme inhibitor, were studied in a rat model of heart failure. Twenty-six rats were divided into two groups: one given 20 mg/kg/day quinapril (n = 11), and controls given 0.5% methylcellulose (n = 15). After oral administration for 1 month, quinapril reduced heart weight (from 1.28+/-0.05 to 0.87+/-0.02 g; p < 0.05) without changing body weight. Quinapril lowered left ventricular end-diastolic pressure (from 14.1+/-2.0 to 6.6+/-1.5 mmHg; p < 0.05) and central venous pressure (from 2.7+/-0.9 to 0.7+/-0.4 mmHg), and increased +/- dP/dt (from +2409+/-50 to +3569+/-169 mmHg/s, and from -2318+/-235 to -3960+/-203 mmHg/s; both p < 0.01). The area of myocardial fibrosis was markedly reduced by quinapril (6+/-3%) as compared with controls (29+/-6%; p < 0.01). Expression of transforming growth factor (TGF)-beta1 mRNA was markedly increased in controls as compared with age-matched normal rats. The increase in level of TGF-beta1 mRNA was significantly suppressed by quinapril (from 17.1+/-6.2 to 9.00+/-2.40; p < 0.05). These observations indicated that quinapril has cardioprotective effects on heart failure, and that the beneficial effects may be partly explained by attenuation of fibrotic response through suppression of TGF-beta1 mRNA expression.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Insuficiência Cardíaca/prevenção & controle , Isoquinolinas/uso terapêutico , RNA Mensageiro/biossíntese , Tetra-Hidroisoquinolinas , Fator de Crescimento Transformador beta/biossíntese , Administração Oral , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Progressão da Doença , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/mortalidade , Isoquinolinas/farmacologia , Masculino , Miocardite/metabolismo , Miocardite/mortalidade , Miocardite/prevenção & controle , Quinapril , RNA Mensageiro/antagonistas & inibidores , Ratos , Ratos Endogâmicos Lew , Fator de Crescimento Transformador beta/antagonistas & inibidores , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta1RESUMO
The cardioprotective effects of bisoprolol were studied in a rat model of severe heart failure induced by autoimmune myocarditis. Twenty-eight days after immunization, Lewis rats were divided into four groups: 0.1 mg/kg/day bisoprolol (Group 0.1), 1.0 mg/kg/day bisoprolol (Group 1) and 10 mg/kg/day bisoprolol (Group 10), and vehicle (0.5% methylcellulose; Group V) (all groups, n = 13). After oral administration for 1 month, heart weight, mean blood pressure, heart rate, central venous pressure, peak left ventricular pressure, left ventricular end-diastolic pressure, +/- dP/dt, and area of fibrosis were measured. Although bisoprolol reduced heart rate (399+/-11/min in Group V, 382+/-10/min in Group 0.1, 348+/-8/min in Group 1 and 302+/-9/min in Group 10) and increased survival (62% in Group V, 69% in Group 0.1, and 100% in Group 1 and Group 10) in a dose-dependent manner, this drug did not change heart weight, the area of myocardial fibrosis or hemodynamic parameters. These observations suggested that bisoprolol may improve survival independently of its effect on left ventricular function by reducing sudden death in patients with severe heart failure.
Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Bisoprolol/uso terapêutico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/prevenção & controle , Antagonistas Adrenérgicos beta/farmacologia , Animais , Bisoprolol/farmacologia , Peso Corporal/efeitos dos fármacos , Fibrose , Insuficiência Cardíaca/patologia , Hemodinâmica/efeitos dos fármacos , Masculino , Miocárdio/patologia , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Endogâmicos Lew , Taxa de Sobrevida , Função Ventricular Esquerda/efeitos dos fármacosRESUMO
The extracts of Trapa bispinosa showed interesting antimicrobial activity against Gram-positive and Gram-negative test organisms and significant cytotoxic activity.
