Efeitos da hipóxia isquemia pré-natal no risco cardiovascular e no comportamento de ratos adultos

Abstract

Perinatal stress can be associated with increased susceptibility to affective disorders. There is evidence that shows a relationship between mental and cardiovascular diseases, suggesting that depression may be a risk factor for acute myocardial infarction and cardiovascular mortality. In the present study, we investigated whether there is an association between prenatal hypoxia, ischemia, depression and late cardiovascular disease. Ischemic hypoxia was induced by clamping the uterine arteries of pregnant rats (Wistar) for 45 minutes, on the 18th day of pregnancy. The same conditions were applied to pregnant rats to form the SHAM group, only without clamping the uterine arteries. In addition, another group of control animal was formed, and those animals did not undergo to any type of manipulation. The analyses of serotonin and its metabolite content in the basal midbrain and in the prefrontal cortex were performed using the high-performance liquid chromatography technique. The analysis of the thickness of the tunica media and the deposition of collagen in the aortal tissues were represented by Hematoxylin and Eosin and Picrosirius red, respectively. The oxidative damage was assessed by protein carbonylation and immunohistochemistry for 8-isoprostane and antioxidant defense by antioxidant enzyme activity (SOD, GPx and catalase). Systemic blood pressure was measured using the non-invasive method of caudal plethysmography, and the study of vascular reactivity to vasodilator and vasoconstrictor agents was performed in the mesenteric arterial bed and in the thoracic aorta. Metabolic studies were performed by analyzing the concentrations of glucose, triglycerides, and total cholesterol in the plasma of animals of each group. The data were analyzed statistically using one-way ANOVA and Tukey's post-test. Data was considered significant with p ≤ 0.05. In hypoxic animals (P120), the results show an endothelial dysfunction associated with vascular remodeling and redox imbalance. In addition, our studies demonstrate metabolic changes in HI animals compared to control groups. These results are consistent with a hypothesis of greater vulnerability of the serotonergic system to perinatal stress and the development of functional and structural changes in the cardiovascular system.