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（申请人提供）：由于怀孕期间的生理和病理生理变化，孕妇过度用盐是很常见的。已证明高盐饮食与血压升高之间存在密切关系。尽管大量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发挥重要作用，但关于母体高盐摄入对胎儿吞咽行为发育影响的信息非常有限、ANG受体亚型-AT1?R和AT2-R、血管稳态以及长期编程对后代心血管调节的影响。值得注意的是，我们的初步研究已经证明了子宫内环境（例如渗透压变化）和激素（例如 ANG II）因素对体液和心血管调节的渗透调节和神经化学机制的胎儿发育的重要性。鉴于此，本申请提出假设： 1) 母亲在怀孕期间的盐摄入量可能会影响 AT1-R / AT2-R，这对出生前后的体液平衡和血管收缩力很重要； 2）妊娠期高盐负荷条件下，RAS可能在胎儿及子代心血管重塑中发挥作用； 3) 妊娠期间母亲高盐摄入条件下，RAS 也可能在盐食欲的发展和编程中发挥关键作用。因此，拟议的研究将确定母体盐负荷对产前和产后生活中AT1-R和AT2-R以及血管收缩力的影响，并确定妊娠期间母体盐负荷对胎儿和后代RAS介导的心血管变化的影响。以及确定 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。获得的数据将为了解妊娠期母体高盐对肾素-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。 项目简介：该项目将确定母亲盐摄入量对子宫内胎儿的急性影响，以及母亲盐饮食对后代盐食欲和心血管稳态的慢性影响。拟议的研究假设肾素-血管紧张素系统（RAS）机制在出生前的行为和心血管发育中发挥作用，并且母体盐的摄入可能会对后代造成印记。值得注意的是，胎儿的高水合是正常的，与 AT2-R 的优势相关，而成人的低水合则伴随着 AT1-R 的优势。研究 ANG 受体的发育与胎儿体内高水合状态之间的联系程度及其在盐负荷条件下的反应至关重要。获得的结果可能会产生与出生相关的盐和水平衡变化相关的从以 AT2-R 为主向以 AT1-R 为主的转变的重要信息。此外，体外血管收缩性研究将确定 RAS 机制参与与不同年龄的胎儿和后代组织中盐负荷相关的血管调节的作用。总之，该项目的重点和综合方法将产生预防医学方面的重要信息，涉及对液体量和心血管稳态至关重要的 RAS 控制的发展，以及母体盐摄入量对子宫内胎儿的急性和慢性影响，并可能在后代身上留下印记。