Adaptação oxidativa e funcional progressiva do sistema cardiopulmonar secundária à hipertensão arterial pulmonar em ratos
AUTOR(ES)
Fabiano Leichsenring Silva
FONTE
IBICT - Instituto Brasileiro de Informação em Ciência e Tecnologia
DATA DE PUBLICAÇÃO
2011
RESUMO
Pulmonary Arterial Hypertension (PAH) is a disease that affects the pulmonary vessels, essentially pre-capillaries, leading to remodeling of the vascular wall. It is characterized hemodynamic syndrome, which is the increase in pulmonary vascular resistance and right ventricular afterload. A growing body of evidence shows the involvement of oxidative stress in the development of the cardiopulmonary changes due to PAH. Thus, the purpose of this study was to evaluate structural changes and time-dependent oxidative stress produced by monocrotaline, a drug that mimics the human PAH, on the rat lung and its impact on late left ventricular cardiac function. Wistar rats with 2 months of age were used in this research. The experimental procedures were divided into two distinct periods: the first step aimed at analyzing lung and the second for cardiac analysis. Induction of PAH was performed by injection of monocrotaline (MCT) 60 mg/kg. At first we investigated morphological changes and oxidative lung at 7 and 21 days after MCT, and the lungs were homogenized for analysis of thiobarbituric acid reactive substances, protein carbonylation, superoxide anion radical by the reaction of nitroblue tetrazolium, activities myeloperoxidase (MPO) and catalase (CAT). After, we analyzed changes in left ventricular (LV) at 7, 21 and 31 days and evaluated LV function by echocardiography and oxidative markers in the LV homogenate by the ratio of glutathione (GSSG / GSH), thioredoxin reeducates (TrxR ), hydrogen peroxide (H2O2) and concentration of vitamin C. Was Observed cardiac hypertrophy, pulmonary congestion and RV in MCT groups 21 and 31 days. The stereology showed a reduction in lung volume and area densities, associated with an increased alveolar space on day 21 after MCT, as well as increased lipid peroxidation in lung homogenate, increased concentration of superoxide anion and increased activity of CAT and MPO. Echocardiography showed wave of change in pulmonary artery flow from 21 days after MCT, and increase in ejection time and the parameters of left ventricular function at 31 days after MCT. The concentration of H2O2 in homogenized LV was increased in MCT groups 21 and 31 days and the analysis of antioxidants observed reduction in the concentration of ascorbic acid and increased TrxR in the LV. Our findings showed increased pulmonary vascular resistance, as well as increased pro-oxidants and oxidative damage to lipids in lung homogenate after 21 days of induction of PAH by MCT, this damage is accompanied by increased activity of CAT and histological pulmonary congestion in this tissue, followed by right ventricular changes. These changes in the right ventricle promoted by the PAH can contribute in the long run, to left ventricular dysfunction observed at 31 days after MCT. These changes are associated with increased LV for hydrogen peroxide and vitamin C reductions in the left ventricular homogenate.
ASSUNTO(S)
hipertensão pulmonar estresse oxidativo monocrotalina espécies reativas de oxigênio doença cardiopulmonar
