Chronic ethanol consumption is a risk factor for cardiovascular diseases. In this sense, the heart is a main target of the deleterious effects of ethanol in the cardiovascular system. Chronic ethanol consumption induces the expression of the enzyme inducible nitric oxide (NO) synthase (iNOS) and increases the generation of reactive oxygen species (ROS) in the heart and these actions lead to tissue damage. Individuals who consume ethanol frequently and who develop sepsis show longer hospitalization periods and higher mortality rates. Sepsis is defined as a dysfunction of an organ, with a potential risk of death, based on a deregulated host response to infection. Sepsis compromises the cardiovascular system leading to irresponsiveness to vasoconstrictors, hypotension, myocardial depression and these responses are mediated by iNOS-derived NO. The experimental model of cecum puncture and ligation (CLP) is widely used to evaluate the impact of sepsis in the cardiovascular system. Experimental studies have shown that sepsis induced by CLP leads to myocardial depression. These studies implicated iNOS as a central mechanism by which sepsis induces its deleterious effects in the heart. In addition, sepsis increases ROS generation and this response may lead to lipoperoxidation and tissue dysfunction. Therefore, both ethanol consumption and sepsis have a negative impact on cardiac structure and function and iNOS seems to be an important element that mediates these responses. However, there are no studies evaluating the impact of ethanol consumption on the cardiac damage induced by sepsis. The hypothesis of this study is that chronic ethanol consumption will induce iNOS expression and ROS generation in the heart, and these responses will lead to tissue damage due to lipoperoxidation, contributing to the increase of cardiovascular dysfunction and susceptibility to sepsis. Therefore, the present project was designed to investigate the impact of ethanol consumption on cardiac damage induced by sepsis and the possible participation of iNOS in this response.
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