Tratamento com alta dose de atorvastatina melhora a função endotelial em ratos diabéticos por diminuição de ROS

• Ano de defesa: 2016
• Autor(a) principal: Simões, Fabiana Vieira
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal do Espírito Santo; BR; Doutorado em Ciências Fisiológicas; Centro de Ciências da Saúde; UFES; Programa de Pós-Graduação em Ciências Fisiológicas
• Palavras-chave em Português: Atorvastatina; Diabetes mellitus; Função vascular; Ciclooxigenase-2; Estresse oxidativo; Fármacos; Diabetes; Rato como animal de laboratório; Fisiologia; 612
• Link de acesso: http://repositorio.ufes.br/handle/10/8018

Because previous studies have conflicting results regarding the effects of statin treatment in diabetes mellitus (DM), the aim of this research was to investigate how treatment with high-dose atorvastatin affects the vascular function in diabetic rats. Wistar rats weighing 220 to 250g, were divided into four groups:1) control group treated only with the vehicle carboxymethylcellulose (Ct); 2) control group treated with atorvastatin 80 mg / kg / day (Ct+At); 3) diabetic group induced by streptozotocin (STZ) treated only with the vehicle carboxymethylcellulose (Db); and 4) diabetic group induced by STZ treated with atorvastatin (Db+At). The treatment was done during four weeks, daily, via gavage. Aortic segments were used to investigate the vascular reactivity, the protein expression of cyclooxygenase-2 (COX-2) and subunit NOX1, and superoxide anions levels. It has been observed that treatment with atorvastatin did not affect glycemia levels in none of the groups. In the diabetic rats, reactivity vascular response to phenylephrine increased when compared to control groups, and treatment with atorvastatin reduced this response in diabetic rats. Removal of the endothelium increased response to phenylephrine in control rats but not in diabetic group; atorvastatin increased endothelial modulation in these rats. The L-NAME (100 uM) increased reactivity in all groups, but this effect was greater in diabetic rats treated with atorvastatin. Indomethacin (10 uM) and NS398 (1mM) decreased the contractile response in diabetic rats and atorvastatin reversed these effects without affecting COX-2 expression. The apocynin (30mM) decreased the response of phenylephrine in diabetic rats, which also showed increased NOX1 and superoxide anion; these effects were prevented by atorvastatin treatment. The results suggest that treatment with high dose of atorvastatin, regardless of glycemia reduces vascular injury and improves endothelial function in aorta from diabetic rats by reducing prostanoids constrictor 2 derivatives. Furthermore, reduced oxidative stress by HADPH oxidase and a possible increased in nitric oxide contribution.