Remodelamento ventricular induzido pelo estresse crônico moderado e imprevisível em ratos: papel da Angiotensina II

• Ano de defesa: 2016
• Autor(a) principal: Firoozmand, Lilia Taddeo [UNIFESP]
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: Stress; Angiotensin II; Left ventricular hypertrophy; Catecholamines; Fibrosis; Estresse; Angiotensina II; Catecolaminas; Fibrose; Hipertrofia ventricular esquerda
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=3669775; https://repositorio.unifesp.br/handle/11600/47875

Chronic stress is an important risk factor for cardiovascular disease. Chronic stress can stimulate angiotensin II that in turn stimulates the development of fibrosis and left ventricular hypertrophy. Our research group has already shown that chronic mild and unpredictable stress (CMS) increases blood pressure and leads to endothelial dysfunction. Thereby, to extend these results the objective of this study was to test the hypothesis that chronic stress induces cardiovascular remodeling, including ventricular hypertrophy and changes in the extracellular matrix components, and that these changes are mediated, at least in part, by the activation of AT1 receptor. Male Sprague-Dawley rats (2 months old) were randonly assigned into: Control, Stress, Control + losartan and Stress + Losartan (n = 6/group, losartan: 20mg/kg/day, AT1 receptor blocker) and all procedures were approved by Ethics Committee on Animal Use of UNIFESP n° 3371130516. The experimental period lasted 7 weeks and the CMUS protocol was applied on weeks 3, 4 and 5. The rats were euthanized 15 days after CMS exposure, and blood samples and left ventricular (LV) were collected for biochemical and histological analysis. Data were analyzed by two-way ANOVA and Tukey test (p<0,05). The results of this study showed that the CMS increased glycemia and and plasma corticosterone, compared to the control group, with no effect of losartan on these parameters. LV catecholamines concentration was similar in both groups. In addition, it was observed an increase of angiotensin II and a reduction of angiotensin 1-7 in the LV, in response to CMS, with a protective effect of losartan. The CMS also induced an increase on the number of chymase mast cells with no influence of AT1 receptor blockade. Morphological analysis showed that CMS induced LV hypertrophy, increased the diameter of cardiomyocytes, interstitial and perivascular collagen, associated with ultrastructural disorganization. On the other hand, AT1 blockade preserved the integrity of ventricular tissue. There were also observed changes in LV microcirculation (capillaries and arterioles) induced by CMS, which were prevented by losartan. The data from this study show that the CMS induce LV hypertrophy associated with tissue and vascular stiffness, structural disorganization, and these changes are mediated in part by activation of the AT1 receptor by angiotensin II.