Abstract
In the last decades, obesity has become a worldwide epidemic. Excess adipose tissue favors the development of associated diseases such as hypertension, obstructive sleep apnea and alveolar hypoventilation. Studies have shown that obesity activates the renin-angiotensin system (RAS), increased serum levels of leptin and the levels of proinflammatory cytokines, including in the central nervous system. However, the pathways and neural mechanisms involved in these responses are not yet fully elucidated. Therefore, the aim of this study is to evaluate the cardiovascular, ventilatory and metabolic changes in rats with high fat diet and to study the possible participation angiotensinergic system and the melanocortin system activated by leptin in the nucleus of the solitary tract (NTS) in these changes. For this, adult Holtzman rats (300-320 g) will undergo a high fat diet (3, 6 and 12 weeks). In each period, we will assess the ventilatory responses during chemoreflex activation in hypoxia (7% O2) and hypercapnia (7% CO2), mean arterial pressure and heart rate at baseline and the baroreflex, before and after the treatment in the NTS with melanocortin MC3 receptor antagonist/4 or changing the RAS within the NTS, by way of losartan (AT1 antagonist) injection into the NTS or by the over-expression of angiotensin II AT2 receptors in the NTS. We will also evaluate the respiratory coefficient, lipid profile, plasma levels of glucose, leptin and insulin. At the end of the experiments, the brains will be removed for gene expression in the NTS of genes related to the RAS, leptin and pro-and antiinflammatory cytokines. (AU)
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