Blockade of AT1 type receptors for angiotensin II prevents cardiac microvascular fibrosis induced by chronic stress in Sprague-Dawley rats

Autor(es)

Firoozmand, Lilia Taddeo ^[1] ; Sanches, Andrea ^[2] ; Damaceno-Rodrigues, Nilsa Regina ^[3] ; Perez, Juliana Dineia ^[1] ; Aragao, Danielle Sanches ^[1] ; Rosa, Rodolfo Mattar ^[1] ; Marcondes, Fernanda Klein ^[2] ; Casarini, Dulce Elena ^[1] ; Caldini, Elia Garcia ^[3] ; Cunha, Tatiana Sousa ^[4]

Afiliação do(s) autor(es)

^[1] Fed Univ Sao Paulo UNIFESP, Dept Med, Sao Paulo - Brazil

^[2] Univ Campinas FOP UNICAMP, Piracicaba Dent Sch, Dept Physiol Sci, Piracicaba - Brazil

^[3] Univ Sao Paulo, Sch Med, Dept Pathol, Lab Cell Biol LIM59, Sao Paulo - Brazil

^[4] Fed Univ Sao Paulo UNIFESP, Dept Sci & Technol, Inst Sci & Technol, Sao Jose Dos Campos - Brazil

• Tipo de documento: Artigo Científico
• Fonte: STRESS-THE INTERNATIONAL JOURNAL ON THE BIOLOGY OF STRESS; v. 21, n. 6, p. 484-493, NOV 2 2018.
• Citações Web of Science: 0

Resumo

To test the effects of chronic-stress on the cardiovascular system, the model of chronic mild unpredictable stress (CMS) has been widely used. The CMS protocol consists of the random, intermittent, and unpredictable exposure of laboratory animals to a variety of stressors, during 3 consecutive weeks. In this study, we tested the hypothesis that exposure to the CMS protocol leads to left ventricle microcirculatory remodeling that can be attenuated by angiotensin II receptor blockade. Male Sprague-Dawley rats were randomly assigned into four groups: Control, Stress, Control + losartan, and Stress + losartan (N = 6, each group, losartan: 20 mg/kg/day). The rats were euthanized 15 days after CMS exposure, and blood samples and left ventricle were collected. Rats submitted to CMS presented increased glycemia, corticosterone, noradrenaline and adrenaline concentration, and losartan reduced the concentration of the circulating amines. Cardiac angiotensin II, measured by high-performance liquid chromatography (HPLC), was significantly increased in the CMS group, and losartan treatment reduced it, while angiotensin 1-7 was significantly higher in the CMS losartan-treated group as compared with CMS. Histological analysis, verified by transmission electron microscopy, showed that rats exposed to CMS presented increased perivascular collagen and losartan effectively prevented the development of this process. Hence, CMS induced a state of microvascular disease, with increased perivascular collagen deposition, that may be the trigger for further development of cardiovascular disease. In this case, CMS fibrosis is associated with increased production of catecholamines and with a disruption of renin-angiotensin system balance, which can be prevented by angiotensin II receptor blockade. (AU)

• Processo FAPESP: 09/13144-5 - Papel do sistema-renina-angiotensina nos efeitos cardiovasculares induzidos por estresse crônico em ratos
• Beneficiário: Andrea Sanches
• Modalidade de apoio: Bolsas no Brasil - Mestrado