Remodelação miocárdica após infarto agudo do miocárdio experimental em ratos: efeito do bloqueio do sistema renina angiotensina aldosterona

Abstract

OBJETIVO: Verificar a ação do lisinopril e do losartan sobre a remodelação miocárdica no infarto experimental em ratos. MÉTODOS: Ratos machos Wistar foram submetidos a infarto e tratados com lisinopril 20 mg/kg/dia (LIS, n=13) ou losartan 20 mg/kg/dia (LOS, n=11), ou mantidos sem tratamento (NT, n=11), por três meses e os resultados comparados com grupo controle (CONT, n=11) de ratos sem infarto. Após a eutanásia, o ventrículo esquerdo foi separado e pesado. Foram medidas a área seccional dos miócitos (AC), fração de colágeno intersticial (CVF) e a hidroxiprolina (HOP) miocárdica. As variáveis foram comparadas pela ANOVA de uma via, para nível de significância de p<0,05. RESULTADOS: O infarto agudo promoveu a hipertrofia do ventrículo esquerdo e os tratamentos com lisinopril e losartam preveniram a hipertrofia quantificada pelo peso do ventrículo esquerdo (LOS=1,06&plusmn; 0,12g, LIS=0,97&plusmn;0,18g, NT=1,26&plusmn;0,17g, CONT=1,02&plusmn; 0,09g; p<0,05), pelo peso de ventrículo esquerdo corrigido pelo peso corporal VE/PC (LOS=2,37&plusmn;0,21mg/g, LIS=2,41&plusmn; 0,38mg/g,NT=2,82&plusmn;0,37mg/g, CONT=2,27&plusmn; 0,15mg/g) e pela medida da AC do ventrículo esquerdo (LOS=210&plusmn;39&micro;², LIS=217&plusmn;35&micro;², NT=256&plusmn;35&micro;², CONT= 158&plusmn;06 &micro;²; p<0,05). O CVF foi significantemente maior no ventrículo esquerdo do grupo infartado e houve prevenção do aumento com os tratamentos (LOS=1,16&plusmn;0,4%, LIS=1,27&plusmn; 0,5%, NT=1,8&plusmn; 0,4%, CONT=0,7&plusmn;0,5%). A HOP foi maior no grupo infartado (NT=6,91&plusmn;2,98mg/g vs. CONT=2,81&plusmn;1,21mg/g) e não alterou com o tratamento. CONCLUSÃO: A remodelação miocárdica pós-infarto é caracterizada por aumento da massa ventricular remanescente e aumento de colágeno intersticial. O bloqueador da enzima conversora da angiotensina e o antagonista seletivo AT1 da angiotensina II previnem a hipertrofia do miócito e a fibrose intersticial.

OBJECTIVE: To assess the effect of lisinopril and losartan on myocardial remodeling in experimental infarction in rats. METHODS: Male Wistar rats underwent myocardial infarction and were either treated with lisinopril [20 mg/kg/day (LIS, n=13)] or losartan [20 mg/kg/day (LOS, n=11)], or kept without any treatment (NT, n=11) for 3 months. Their results were compared with those of a control group (CONT, n=11) comprising noninfarcted rats. After euthanasia, the left ventricle was isolated and weighed. The following measurements were taken: the sectional area of myocytes (AC), interstitial collagen fraction (CVF), and myocardial hydroxyproline (HOP). The variables were compared by using 1-way ANOVA, with a significance level of P<0.05. RESULTS: Acute myocardial infarction caused left ventricular hypertrophy. The treatments with lisinopril or losartan could prevent hypertrophy, which was quantified by use of left ventricular weight (LOS=1.06&plusmn;0.12g, LIS=0.97&plusmn;0.18g, NT=1.26&plusmn;0.17g, CONT=1.02&plusmn;0.09g; P<0.05), of left ventricular weight-to-body weight ratio LV/BW (LOS=2.37&plusmn; 0.21mg/g, LIS=2.41&plusmn;0.38mg/g, NT=2.82&plusmn;0.37mg/g, CONT=2.27&plusmn; 0.15mg/g), and of left ventricular AC measure-ment (LOS=210&plusmn;39&micro;², LIS=217&plusmn;35&micro;², NT=256&plusmn;35&micro;², CONT=158&plusmn;06 &micro;²; P<0.05). The CVF was significantly greater in the left ventricle of the infarcted group, and its increase was prevented with treatment (LOS=1.16&plusmn;0.4%, LIS=1.27&plusmn;0.5%, NT=1.8&plusmn; 0.4%, CONT=0.7&plusmn;0.5%). Myocardial hydroxyproline was greater in the infarcted group (NT=6.91&plusmn;2.98mg/g vs. CONT=2.81&plusmn; 1.21mg/g) and did not change with treatment. CONCLUSION: Myocardial remodeling after infarction is characterized by an increase in the remaining ventricular mass and in interstitial collagen. The angiotensin-converting-enzyme blockers and the selective angiotensin II AT1 antagonist prevent hypertrophy of the myocyte and interstitial fibrosis.