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Efeitos da rosuvastatina e olmesartana sobre o remodelamento de aorta, miocárdio e rim em ratos hipertensos por deficiência crônica da síntese de óxido nítrico

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Previous issue date: 2011-06-09 / Alterações no remodelamento miocárdico, vascular, inflamatório, proteinúria e inflamação glomerular em ratos deficientes de óxido nítrico (NO), tratados com olmesartana medoxomila (OLM) e/ou rosuvastatina cálcica (ROS) foram estudadas após 28 dias com o objetivo de avaliar o impacto destes fármacos. Veículo (G1), Lnitro-arginina-metil-éster (L-NAME) 30mg/kg/dia (G2), OLM 5mg/kg/dia (G3), ROS 20mg/kg/dia (G4), OLM 0,5mg/kg/dia (G5), ROS 2mg/kg/dia (G6), OLM 0,5+ROS 2mg/kg/dia (G7), OLM 5+ROS 20mg/kg/dia (G8) administrados oralmente a ratos Wistar. Pressão sistólica (PS) mensurada semanalmente. Análises hematológica, bioquímica {colesterol total (CT), triglicérides (Tg), aminotransferases (AMT), fosfatase alcalina (FA), creatinina (Cr), nitrito/nitrato (NOx), Interleucina-6 (IL-6), Fator de Necrose Tumoral-alfa (TNF-α)}, urinária: {relação albumina/creatinina (RACU)}. Cortes de ventrículo esquerdo, aorta, rins (hematoxilina/eosina e Masson), analisados morfometricamente: análise transversa de cardiomiócitos (ATC), relação média e íntima sobre o lúmen arterial (MILA), fibrose perivascular de arteríolas intramiocárdicas (FPAI). Macrófagos glomerulares (MG) analisados por imunohistoquímica. L-NAME elevou a PS, ATC, MILA, FPVAI, IL-6, MG (p < 0,0001), TNFα, RACU, reduziu NOx (p < 0,01). OLM reduziu PS (p < 0,001), TNF-α (p < 0,05), IL6, ATC, MILA, FPVAIM (p < 0,0001), MG (p < 0,01), RACU (G3) (p < 0,05). ROS elevou NOx (G6), reduziu TNF-α, RACU (G4) (p< 0,05), IL-6, ATC, MILA (G4), FPAI (p < 0,0001), MG (p < 0,001). ROS potencializou efeito de OLM sobre a RACU. OLM e ROS exercem efeitos benéficos no remodelamento miocárdico, vascular, inflamatório e renal em ratos deficientes de NO. Efeitos pleiotrópicos de ROS independentes da PS e CT, mediados por suas propriedades antioxidantes / Changes in myocardial remodeling, vascular inflammation, proteinuria, and glomerular inflammation in nitric oxide (NO)-deficient rats, treated with olmesartan medoxomil (OLM) and / or rosuvastatin calcium (ROS) were studied after 28 days in order to assess the impact of these drugs. Vehicle (G1), nitro-L-arginine methyl ester (L-NAME) 30mg/kg/dia (G2), OLM 5mg/kg/day (G3), ROS 20mg/kg/day (G4), OLM 0,5mg/kg/day (G5), ROS 2mg/kg/day (G6), OLM 0.5+ROS 2mg/kg/day (G7), OLM 5+ROS 20mg/kg/day (G8) orally administered to Wistar rats. Systolic pressure (SBP) measured weekly. Haematological, biochemical {total cholesterol (TC), triglycerides (Tg), aminotransferase (AMT), alkaline phosphatase (ALP), creatinine (Cr), nitrite / nitrate (NOx), Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNFα)}, urinary {albumin / creatinine ratio (UACR)}. Cuts from the left ventricle, aorta, kidneys (hematoxylin / eosin and Masson) were morphometrically analyzed: crosssectional area of cardiomyocytes (Acmy), intima-media thickness on the arterial lumen (IMT), perivascular fibrosis of intramyocardial arterioles ratio (PFR). Glomerular macrophages (GM) were analyzed by immunohistochemistry. L-NAME increased the SBP, Acmy, IMT, PFR, IL-6, GM (p <0.0001), TNF-α, UACR reduced NOx (p <0.01). OLM reduced SBP (p <0.001), TNF-α (p <0.05), IL-6, Acmy, IMT, PFR (p <0.0001), GM (p <0.01), UACR (G3) (p <0.05). ROS increased NOx (G6), reduced TNF-α, UACR (G4) (p <0.05), IL-6, Acmy, IMT (G4), PFR (p <0.0001), GM (p <0.001). ROS potentiated the effect of OLM on UACR. OLM and ROS exert beneficial effects on myocardial, vascular, inflammatory and renal remodeling in nitric oxide deficient rats. The pleiotropic effects of ROS were independent of SBP and TC, mediated by its antioxidant properties.

Identiferoai:union.ndltd.org:IBICT/oai:hermes.cpd.ufjf.br:ufjf/3863
Date09 June 2011
CreatorsGirardi, José Marcos
ContributorsRaposo, Nádia Rezende Barbosa, Ferreira, Ana Paula, Magalhães, Maria Eliane Campos, Oliveira, Glaucia Maria Moraes de
PublisherUniversidade Federal de Juiz de Fora (UFJF), Programa de Pós-graduação em Saúde Brasileira, UFJF, Brasil, Faculdade de Medicina
Source SetsIBICT Brazilian ETDs
LanguagePortuguese
Detected LanguagePortuguese
Typeinfo:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/doctoralThesis
Sourcereponame:Repositório Institucional da UFJF, instname:Universidade Federal de Juiz de Fora, instacron:UFJF
Rightsinfo:eu-repo/semantics/openAccess

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