Zornoff L A, Paiva S A, Matsubara B B, Matsubara L S, Spadaro J
Departamento de Clínica Méedica, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista-Brazil.
J Cardiovasc Pharmacol Ther. 2000 Jul;5(3):203-9. doi: 10.1054/JCPT.2000.7450.
There are limited data regarding the effects of angiotensin II receptor blockade after myocardial infarction (MI). In addition, whether combined angiotensin converting enzyme (ACE) inhibitor and angiotensin II type I (AT(1)) receptor antagonist may be superior to either drug alone on ventricular remodeling remains unclear. The goal of this study was to determine if the cardiac effects of the combined administration of an ACE inhibitor and AT(1) receptor antagonist are greater than those produced by either of these agents administered individually after MI.
After MI, rats were divided into 4 groups: 1) untreated animals, 2) lisinopril treatment (20 mg/kg/day), 3) losartan treatment (20 mg/kg/day), and 4) lisinopril plus losartan treatment. After 3 months, the cardiac parameters studied were: mortality, fibrosis (hydroxyproline), hypertrophy (ventricular weight/body weight ratio [VW/BW]), left ventricular enlargement (volume at end-diastolic pressure equaled zero/body weight ratio [V0/BW]), and ventricular function (isovolumetric developed pressure, dp/dt, -dp/dt). A lowest mortality rate in the animals treated with the combination of both ACE inhibitor and AT(1) receptor antagonist was observed. Although lisinopril and losartan significantly decreased VW/BW ratio, when administered concomitantly, VW/BW ratio was lower than when either agent was administered individually. There were no differences in right ventricle hydroxyproline concentration. Only combination therapy decreased V0/BW ratio. The treatment with lisinopril plus losartan resulted in increases in the development of pressure versus untreated group; without alteration in dp/dt and -dp/dt.
The combination of the AT(1) receptor blockade and ACE inhibitor is more effective than individual treatment on ventricular remodeling and survival after MI in rats.
关于心肌梗死（MI）后血管紧张素II受体阻断的作用，相关数据有限。此外，血管紧张素转换酶（ACE）抑制剂与血管紧张素II 1型（AT(1)）受体拮抗剂联合使用在心室重构方面是否优于单独使用任一药物仍不清楚。本研究的目的是确定MI后联合使用ACE抑制剂和AT(1)受体拮抗剂的心脏效应是否大于单独使用这两种药物中的任何一种所产生的效应。
MI后，将大鼠分为4组：1）未治疗动物；2）赖诺普利治疗组（20 mg/kg/天）；3）氯沙坦治疗组（20 mg/kg/天）；4）赖诺普利加氯沙坦治疗组。3个月后，研究的心脏参数包括：死亡率、纤维化（羟脯氨酸）、肥大（心室重量/体重比[VW/BW]）、左心室扩大（舒张末期压力等于零时的容积/体重比[V0/BW]）和心室功能（等容收缩压、dp/dt、-dp/dt）。观察到联合使用ACE抑制剂和AT(1)受体拮抗剂治疗的动物死亡率最低。虽然赖诺普利和氯沙坦显著降低了VW/BW比值，但联合使用时，VW/BW比值低于单独使用任一药物时。右心室羟脯氨酸浓度无差异。只有联合治疗降低了V0/BW比值。赖诺普利加氯沙坦治疗导致压力发展较未治疗组增加；dp/dt和-dp/dt无变化。
在大鼠MI后，AT(1)受体阻断与ACE抑制剂联合使用在心室重构和生存方面比单独治疗更有效。
