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Study of hemodynamic, inflammatory, histological and oxidative stress effects after exposure to diesel exhaust fuel: experimental model in hypertensive rats

Abstract

Cardiovascular diseases are the leading causes of death in Brazil, and have become common in modern societies due to contemporary lifestyles in the developed world. Among the causes of increased cardiovascular mortality are the environmental risk factors, such as exposure to inhalable particles produced by motor vehicles. Among the chronic diseases that present a significant endothelial dysfunction and oxidative stress as likely regulators of vascular homeostasis breakdown of hypertension is considered the most important for the occurrence of cardiovascular disease risk factor. Globally, hypertension is responsible for at least 45% of deaths from heart disease and 51% of deaths from stroke. Knowing that exposure to urban particles is related in a direct way with the production of oxidative stress, it is plausible that urban pollution in large cities may favor the development or even aggravate the condition of hypertension. The opportunity to study the direct effect of the exhaust from the combustion of diesel in rodents products is extremely important and effective means of intoxication model with the generator fuel installed in the Faculty of Medicine of the USP campus. In an unprecedented way in Brazil, the system enables fuel generator assess toxicological risks of fuels and their mixtures in a wide range of outcomes. Our main proposal to evaluate the hemodynamic effects, aspects of remodeling of the cardiac extracellular matrix fibers (collagenous and elastic system system), pulmonary inflammatory profile and cardiac and pulmonary oxidative stress in order to obtain a connection between pulmonary exposure to diesel and its effects systemic, including the integration of the cardiovascular system in experimental models of hypertension. For this purpose, the following parameters will be evaluated: heart rate, heart rate variability, blood pressure, bronchoalveolar lavage; complete blood count, platelets, reticulocytes and coagulation factors (thrombogenic: fibrinogen and von Willebrand factor, and antitrombogêncios: anti-thrombin III and activated protein C); expression of markers of oxidative stress (gp91phox) and nitrosative (iNOS, 3-nitrotyrosine) and 8-isoprostane by peribronchial cells, perivascular and parenchymal lung, vascular endothelium of peribronchiolar and cardiac vessels by immunohistochemistry; activity of the enzymes NADPH oxidase, superoxide dismutase SOD-, isoforms (SOD-1, SOD-2 and SOD-3), glutathione peroxidase (GPX) and catalase (CAT) in bronchoalveolar lavage fluid using immunoassay and qualitative and quantitative assessment (by stereological techniques), the fibrillar elements in the remodeling of extracellular matrix (collagenous and elastic system) of the left ventricle of SHR. (AU)