Ação da inibição da enzima conversora da angiotensina em aorta, fígado, rim e pâncreas em condições de hipercolesterolemia e hiperglicemia induzidas experimentalmente

• Ano de defesa: 2010
• Autor(a) principal: Pomaro, Daniel Roberto [UNIFESP]
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• dARK ID: ark:/48912/001300001cpz4
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: Hypercholesterolemia experimentally induced; Diabetes Mellitus; Arteriosclerosis; Cholesterol; Angiotensin-converting enzyme inhibitors; Diabetes Mellitus, Experimental; Rabbits; Colesterol; Inibidores da enzima conversora da angiotensina; Arteriosclerose; Diabetes Mellitus experimental; Coelhos
• Link de acesso: https://repositorio.unifesp.br/handle/11600/8862

Diabetes Mellitus is a major risk factor for vascular disease and the imbalance of the renin-angiotensin system exerts deleterious effects on various organs, further the use of ACE inhibitor or AT1 receptor blockers may exerts a beneficial effect. Objective: We performed a retrospective study where the effect of an ACE inhibitor, quinapril, on changes in target organs such as aorta, liver, kidney and pancreas of diabetic and hypercholesterolemic rabbits was analyzed. Methods: We performed a retrospective study on tissue samples of aorta, liver, kidney and pancreas of alloxan-induced diabetic rabbits which have also become hypercolesterolemic through a rich cholesterol fed. The animals were divided into four groups according to glucose levels (Group I = 432 ± 45 mg / dL, Group II = 514 ± 40 mg / dL, Group III = 149 ± 09 mg / dL, Group IV = 156 ± 10 mg / dL). The rabbits in groups II and IV received quinapril (30 mg/day) in their food and all animals received a diet enriched with 0.5% cholesterol for 12 weeks. The following parameters were analyzed: in the aorta – the immunohistochemical expression of MCP-1 and ICAM-1, and an in vitro assay using endothelial cells of rabbit aorta by analyzing the expression thereof were analyzed. In the kidney – it was analyzed the histopathology, histomorphometry and the immunostaining of macrophages, MCP-1 and ICAM- 1. In the liver – we performed a histopathological analysis and the evaluation of fibrosis was accessed by image analysis. In the pancreas – it was analyzed the histopathologic and the histomorphometric changes and an in vitro assay using isolated islets from rabbits was performed to evaluate the oxidative stress. Results: In the aorta there was a reduction in the immunohistochemical expression of ICAM-1 by treatment with ACE inhibitors in both tissue and endothelial cells cultured, however, this reduction was abolished in the presence of high concentrations of glucose. The immunohistochemical expression of MCP-1 was lower in animals treated with ACE inhibitors, but in cell culture the immuno-expression was not modified by treatment with ACE inhibitors, but by the concentration of glucose in the medium. In the kidney, the use of an ACE inhibitor attenuated the glomerular lesions and reduced the immunohistochemical expression of ICAM-1 and MCP-1. In the liver, the use of an ACEI reduced hepatic fibrosis, but this protective effect was not significant in animals hyperglycemic. In the pancreas, the ACEI treatment did not protect the islets destroyed by alloxan, but in the in vitro assay the oxidative stress was reduced. Conclusion: We found that the ACE inhibitor attenuated the changes in the kidney, but in aorta, liver and isolated pancreatic islets this protection depends on glycemic control.