Overuse of salt is common by pregnant women due to physiological and pathophysiological changes during pregnancy. A strong relationship between high salt diet and increased blood pressure (BP) has been demonstrated. Although a number of studies have demonstrated that angiotensin II (ANG II) and its receptors play an important role in salt intake and BP controlling in adults, there is very limited information on the effects of maternal high salt ingestion on the development of fetal swallowing behavior, ANG receptor subtypes-AT1?R and AT2-R, and vascular homeostasis, as well as long-term programming influence on cardiovascular regulation in the offspring. Notably, our preliminary studies have demonstrated the importance of the in utero environmental (e.g., osmotic change) and hormonal (e.g., ANG II) factors on the fetal development of osmoregulatary and neurochemical mechanisms for body fluid and cardiovascular regulation. In light of these, this application hypothesizes: 1) Maternal salt intake during pregnancy may affect AT1-R / AT2-R that are important to body fluid balance and vascular contractility before and after birth;2) The RAS may play a role in cardiovascular remodeling in the fetus and offspring under conditions of high salt loading during pregnancy;3) The RAS also may play a critical role in the development and programming of salt appetite under conditions of maternal high salt intake during pregnancy. Therefore, the proposed studies will determine the effects of maternal salt loading on AT1-R and AT2-R and vascular contractility in prenatal and postnatal life, and determine the RAS- mediated cardiovascular changes in the fetus and offspring to maternal salt loading during pregnancy, as well as determine the effect of AT1-R / AT2-R agonists on age-dependent swallowing and programmed salt appetite. The data gained will add important information to understanding of influence of maternal high salt in pregnancy on renin-angiotensin system mediated remolding of swallowing behavior, vascular contractility, and salt appetite in developmental origin. Project Narrative: This project will determine the acute effect of maternal salt intake on the fetus in utero, and the chronic influence of maternal salt diet on the offspring's salt appetite and cardiovascular homeostasis. The proposed study postulates that renin-angiotensin system (RAS) mechanisms are functional in behavioral and cardiovascular development prior to birth, and that maternal salt intake may cause imprinting on the offspring. Notably, high hydration is normal in fetuses associated with a preponderance of AT2-R, while low hydration of adults is accompanied by a preponderance of AT1-R. It is of utmost importance to investigate the extent to which there is any link between the development of the ANG receptors and high hydration status in the fetal body, as well as their responses, under conditions of salt loading. The results gained may generate significant information on the shift from predominantly AT2-R to predominantly AT1-R associated with birth-related change in salt and water balance. In addition, in vitro vascular contractility studies will determine the effect of RAS mechanisms involved in vascular regulation related to salt loading in fetal and offspring tissues at various ages. Together, the focused and integrated approaches of this project will yield important information in preventive medicine, regarding the development of the RAS controlling that is critical for fluid volume and cardiovascular homeostasis, and acute and chronic effects of maternal salt intake on the fetus in utero, and possibly on the imprinting in the offspring.
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