Salt appetite & vascular remodeling in fetal origin

盐食欲

• 批准号: 7353583
• 负责人: ZHICE XU
• 金额: $ 34.63万
• 依托单位: LOMA LINDA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7353583
• 关键词: ANG gene; Accounting; Acute; Adult; Affect; Age; Agonist; Angiotensin II; Anorexia; Arteries; Barker Hypothesis; Behavior; Behavioral; Birth; Blood Pressure; Blood Vessels; Body Fluids; Body Water; Body Weight; Cardiovascular Physiology; Cardiovascular system; Chemicals; Chronic; Consumption; Coronary heart disease; Data; Deglutition; Dehydration; Desire for food; Development; Diabetes Mellitus; Diarrhea; Diet; Disease; Equilibrium; Fatigue; Fetal Development; Fetus; Fluid Balance; Habits; Health; Hemorrhage; Homeostasis; Hormonal Change; Human; Hydration status; Hypertension; Hypoxia; In Vitro; Incidence; Individual; Ingestion; Laboratories; Life; Light; Link; Liquid substance; Malnutrition; Mammals; Mediating; Mothers; Neurosecretory Systems; Pathogenesis; Physiological; Play; Population; Pregnancy; Pregnant Women; Preventive Medicine; Program Development; Recording of previous events; Regulation; Renin-Angiotensin System; Resistance; Role; Secondary Hypertension; Sodium; Sodium Chloride; Staging; Stroke; Symptoms; Taste Perception; Tissues; Vascular remodeling; Ventricular; Vomiting; Water; age related; base; blood pressure regulation; fetal; imprint; in utero; insight; interest; neurochemistry; offspring; postnatal; prenatal; prenatal influence; programs; receptor; repaired; response; salt intake

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：由于怀孕期间的生理和病理生理变化，过量使用盐是孕妇常见的。高盐饮食与血压升高之间的密切关系已被证实。尽管许多研究表明血管紧张素II （ANG II）及其受体在成人盐摄入和血压控制中起重要作用，但关于母体高盐摄入对胎儿吞咽行为发育的影响的信息非常有限，ANG受体亚型at1 ？R和AT2-R，血管稳态，以及对后代心血管调节的长期编程影响。值得注意的是，我们的初步研究已经证明了子宫内环境（如渗透改变）和激素（如ANG II）因素对胎儿渗透调节和体液和心血管调节的神经化学机制的重要性。鉴于此，本应用假设：1)孕妇在怀孕期间的盐摄入量可能影响AT1-R / AT2-R，这对出生前和出生后的体液平衡和血管收缩性至关重要；2)妊娠期高盐负荷条件下RAS可能在胎儿和子代心血管重构中发挥作用；3) RAS也可能在孕期孕妇高盐摄入条件下盐食欲的发育和规划中发挥关键作用。因此，拟开展的研究将确定母体盐负荷对产前和产后生活中AT1-R、AT2-R和血管收缩性的影响，确定妊娠期间母体盐负荷对RAS介导的胎儿和后代心血管变化，以及AT1-R / AT2-R激动剂对年龄依赖性吞咽和程序性盐食欲的影响。这些数据将为了解孕妇高盐对肾素-血管紧张素系统介导的吞咽行为重塑、血管收缩性和发育起源中的盐食欲的影响提供重要信息。