Papel do 17 β-estradiol no modelo de hipertrofia cardíaca induzida pelo isoproterenol em ratas

Abstract

The role of estrogen in isoproterenol-induced cardiac hypertrophy model is not often studied so far. Therefore, the main purpose of this study was to investigate the best protocolo of isoproterenol-induced cardiac hypertrophy and assess the role the 17 β- estradiol in this model. In the first part female Wistar rats were treated with different doses of D-L isoproterenol chloride: 0,5 (Iso 0,5), 5 (Iso 5), 10 ( Iso 10) mg/kg/day, or vehicle (saline 0.9%) s.c., during 8 or 16 days (n = 10/group). The electrocardiography (ECG), echocardiogram (ECO) and histology were performed in the end of the experiments (8 or 16 days). In second part, female Wistar rats were ovariectomized (Ovx) or false operated (sham) and 48 hours after were treated with isoproterenol (5mg/kg/day), s.c. or vehicle (saline 0.9%) during 16 days (n=10/ group) comprising the groups as follow: sham+saline, Ovx+saline, sham+iso e Ovx+iso. Four additional groups were treated with estradiol benzoate: 7 μg/kg/day (Ovx+E2.7+iso e Ovx+E2.7) or 140 μg/kg/day (Ovx+E2.140+iso) during 16 days (n = 10/group). The dose of isoproterenol was divided into twice a day while estrogen administration once a day. Two weeks before the beginning of the experiments,the rats underwent estrous cycle assessment and those which did not present three consecutive regular cycles were excluded from the study. ECG, and post- mortem studies were performed in the end of the experiments. The groups ISO-0.5, ISO-5 and ISO-10 showed a significant increase in cardiac index when compared to control groups (p < 0,01). The groups treated with isoproterenol during 16 days showed cardiac indexes higher than those treated with the same doses but during 8 days (p < 0,05). ECG showed increase QRS index only in the ISO-5 and Iso -10 groups. The groups treated with isoproterenol showed subendocardic fibrosis, especially in the left ventricle. In second part of this study, the groups treated with isoproterenol showed a significant increase in cardiac index (IC) when compared to control groups. O Ovx+E2.140+iso showed significant increase in IC when compared to Ovx+iso (p < 0,05).The cardiac hypertrophy induced by isoproterenol was time but not dose-dependent, at least in the dose used herein. The fibrosis seems be dose-dependent from the use of bigger doses. High dose of 18-beta estradiol enhanced isoproterenol-induced cardiac hypertrophy which was not detected by conventional ECG assessment.