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Fetal programming induced by exercise during pregnancy and fetal modulation of components of the renin-angiotensin system and kallikrein-kinin system

Grant number: 12/12924-0
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): September 01, 2012
Effective date (End): December 31, 2013
Field of knowledge:Biological Sciences - Biophysics - Biophysics of Processes and Systems
Principal Investigator:Ronaldo de Carvalho Araújo
Grantee:Aline Midori Arakaki
Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil


Epidemiological and animal studies have suggested that early nutritional experiences of the individual can affect the fetus' susceptibility to developing chronic diseases related to metabolic syndrome as an adult. This phenomenon is called metabolic imprinting or fetal reprogramming. These metabolic changes may affect two systems that control blood pressure, the renin-angiotensin system (RAS) and Kallikrein-Kinin System (KKS). Besides the key role in cardiovascular homeostasis by controlling the fluid balance and vascular tone, the SRA is very important during pregnancy because it acts in the control of uteroplacental blood flow. It also has an important role in the local inflammatory response in the endometrium, angiogenesis (increased uterine vasculature), and hemodynamic remodeling. Therefore changing the composition of SARS in uterine tissue during pregnancy is associated with changes in fetal growth and differentiation of the uterus. Additionally, abnormal conditions of the RAS may affect the kidney leading to a decrease in their weight in relation to the bodyweight of the newborn and also a reduction in the number of glomeruli at birth resulting in a hyperfiltration with increased glomerular pressure. In summary, these results show that there is an association between renal changes in the fetus caused by changing the uterine environment and increased incidence of hypertension in adults. As with the SRA, KKS components are also present in the placenta and act on the regulation of the placental. In pregnancy, the RAS is responsible for increased cardiac output and uterine blood flow. However, blood pressure decreases during pregnancy because of the reduction in peripheral vascular resistance associated with the predominance of vasodilator components of the KKS such as bradykinin and nitric oxide (NO) on vasoconstrictors. Furthermore, studies show that this system is related to the implementation and regulation of placental blood flow. Our group is studying whether exercise during pregnancy can lead to cardiovascular disease as occurs in adult offspring of undernourished pregnant. This research was initially proposed due to the fact that maternal exercise and fewer nutrients are available to the fetus. So is there a nutritional competition, because the fetus has to share with the mother oxygen and nutrients to meet their needs during exercise. Studies showed that exercise during pregnancy causes a decrease in the size of fetal birth, reducing the size of the umbilical cord and placental size. However, no study was published evaluating the proteins of the Renin-Angiotensin System (RAS) and Kallikrein-Kinin System (KKS) in mothers who exercise during pregnancy. Also, there is no accounts of how a mother can change these systems may or may not contribute to fetal growth retardation and the development of cardiovascular disease in the offspring. Therefore this project aims to assess the fetal programming induced by exercise during pregnancy and the modulation of the components of Renin-Angiotensin and Kallikrein-Kinin in maternal and offspring. Our objective is to contribute knowledge in this area, which is still very scarce, and clarify some questions regarding the curse/benefit of exercise during pregnancy. We intend thereby to suggest a non-pharmacological method for the prevention of cardiovascular diseases.(AU)

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