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    As Implicações Da Restrição De Crescimento In Utero Sobre A Reatividade Vascular E As Células Progenitoras Endoteliais Em Ratos Wistar: O Papel Do Treinamento Aeróbio
    (Universidade Federal de São Paulo (UNIFESP), 2017-06-30) Oliveira, Vanessa Aparecida De [UNIFESP]; Franco, Maria Do Carmo Pinho [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Intrauterine growth restriction (IUGR) can induce deleterious changes in the modulatory ability of the vascular endothelium, contributing to an increased risk of developing cardiovascular diseases in the long term. However, the mechanisms by which IUGR promotes these changes are not elucidated. Considering the functional properties of endothelial progenitor cells (EPCs) in promoting endothelial repair our first hypothesis is that negative adaptations in EPCs may be involved in endothelial dysfunction induced by IUGR. Therefore, our goals were to investigate the effects of IUGR on vascular reactivity in aortic artery, number, functional properties and senescence process of in vitro CPEs in adult male offspring. For this, pregnant Wistar rats received ad libitum diet or 50% of diet ad libitum during the gestational period. Our results showed that offspring submitted to IUGR had a significant reduction of acetylcholine (ACh) -mediated vasodilation in the thoracic aorta rings, which may be, in part, to the lower concentration of nitric oxide (NO) observed in this vascular bed. The number of circulating and bone marrow EPCs was similar between the experimental groups. However, in vitro functional capacity of circulating CPEs and bone marrow was reduced in the restricted group compared to controls. Additionally, we observed that the restricted animals presented a significant increase in the number of senescent EPCs in the bone marrow vs control group. Therefore, this set of data demonstrates that IUGR can induce endothelial dysfunction in male offspring, which may be due in part to the reduction in NO concentration as well as the lower EPCs repair capacity. Based on these findings, and considering that aerobic training (AT) can induce beneficial effects on vascular function and on the functional capacity of CPEs, our second hypothesis is that the TA could reverse the deleterious adaptations in vascular function and in EPCs in IUGR rats. Therefore, we evaluated the effects of AT on vascular reactivity in aortic artery, number, functional properties and senescence process of in vitro EPCs in adult male offspring submitted to IUGR. Adult male offspring were divided into groups: sedentary control, trained control, restricted sedentary and restricted training. After AT protocol (60 minutes / day, 5 times / weeks, 10 weeks, intensity 50-60% of maximum speed). We observed that AT was effective in restoring ACh-induced vasodilatation in the thoracic aorta of restricted animals, this improvement was associated with normalization of NO concentration. The number of EPCs in bone marrow was reduced in trained control group compared to sedentary. The AT restored the functional capacity in vitro of circulating and bone marrow-derived EPCs in restricted group, which may be associated to the normalization of the number of senescent EPCs in bone marrow in these animals. Therefore, beneficial TA-induced adaptations in restricted animals in utero provide evidence that AT may be a non-pharmacological approach to reverse the negative adaptations in IUGR-induced vasculature and CPEs.