Oxidative stress is increased in skeletal muscle during heart failure (HF) and can contribute to HF-associated skeletal myopathy. However, sources of reactive oxygen species (ROS) and signaling pathways involved in ROS-induced skeletal muscle changes are not completely established. NADPH oxidase is an important source of ROS. Studies have suggested that the signaling pathways of mitogen-activated protein kinases (MAPKs) and nuclear factor-ºB (NF-ºB) can be involved in muscle response to oxidative stress. Physical exercise is an important non-pharmacological therapy to prevent and rehabilitate patients with cardiovascular diseases. One of the important beneficial effects of exercise is related to its antioxidant effect, as it increases antioxidants enzymes and decreases pro-oxidant enzymes expression. There are few studies examining the effects of physical exercise in experimental HF induced by aortic stenosis. The aim of this study is to evaluate the influence of aerobic exercise on oxidative stress and protein expression of MAPK and NF-ºB pathways in skeletal muscle of rats with aortic stenosis-induced HF. Wistar rats weighing 90-100 g will be subjected to thoracotomy to induce aortic stenosis and assigned to four groups: sedentary Sham (Sham-S), exercised Sham (Sham-Ex), sedentary aortic stenosis (AS-S) and exercised aortic stenosis (AS-Ex). The exercised groups will be subjected to treadmill exercise, five times a week for eight weeks. Exercise tolerance will be assessed before and after the training period, by maximal exercise test. Transthoracic echocardiogram will be performed before and after training period. During euthanasia we will evaluate pathological features of HF. Activity of antioxidant enzymes in the soleus muscle will be quantified by spectrophotometry. NADPH oxidase activity and total ROS generation will be assessed by quantifying products derived from the oxidation of dihidroetidio by HPLC. Gene expression of NADPH oxidase subunits will be analyzed by real time RT-PCR. Protein expression of MAPK and NF-ºB pathways will be measured by Western blot. Statistical analysis: ANOVA and Tukey.
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