Salt appetite & vascular remodeling in fetal origin

盐食欲

• 批准号: 7851245
• 负责人: ZHICE XU
• 金额: $ 35.31万
• 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 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7851245
• 关键词: 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（由申请方提供）：由于妊娠期间的生理和病理生理变化，孕妇过度使用盐是常见的。高盐饮食和血压升高之间的密切关系已被证明。尽管大量研究表明血管紧张素II（angiotensin 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研究非常有限。R和AT 2-R，和血管稳态，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，血管紧张素Ⅱ（ANG Ⅱ）因子对胎儿发育的调节作用以及体液和心血管调节的神经化学机制。据此，本申请提出以下假设：1）母亲在怀孕期间的盐摄入可能影响AT 1-R /AT 2-R，这对出生前后的体液平衡和血管收缩性是重要的：2）RAS可能在怀孕期间高盐负荷条件下在胎儿和后代的心血管重构中起作用; 3）RAS在母体妊娠期高盐摄入条件下也可能在盐食欲的发展和编程中起关键作用。因此，拟定的研究将确定母体盐负荷对产前和产后AT 1-R和AT 2-R以及血管收缩性的影响，并确定妊娠期间母体盐负荷对胎儿和后代的RAS介导的心血管变化，以及确定AT 1-R /AT 2-R激动剂对年龄依赖性吞咽和程序性盐食欲的影响。所获得的数据将增加重要的信息，了解母亲在怀孕期间高盐对肾素-血管紧张素系统介导的吞咽行为，血管收缩性和盐食欲的发育起源重塑的影响。 项目叙述：该项目将确定母体盐摄入对子宫内胎儿的急性影响，以及母体盐饮食对后代盐食欲和心血管稳态的慢性影响。这项拟议的研究假设，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起作用，母体的盐摄入量可能会对后代造成印记。值得注意的是，高水合作用在胎儿中是正常的，与AT 2-R的优势相关，而成人的低水合作用伴随着AT 1-R的优势。研究ANG受体的发育与胎儿体内的高水合状态之间的联系以及它们在盐负荷条件下的反应是至关重要的。所获得的结果可能会产生重要的信息，从主要AT 2-R的转变，主要AT 1-R与出生相关的盐和水平衡的变化。此外，体外血管收缩性研究将确定RAS机制在不同年龄的胎儿和后代组织中与盐负荷相关的血管调节中的作用。总之，该项目的重点和综合方法将产生重要的预防医学信息，关于RAS控制的发展，这对液体体积和心血管稳态至关重要，以及母体盐摄入对子宫内胎儿的急性和慢性影响，并可能对后代的印记。

项目成果

High-salt diets during pregnancy affected fetal and offspring renal renin-angiotensin system.

• DOI: 10.1530/joe-13-0139
• 发表时间: 2013-07
• 期刊: The Journal of endocrinology
• 作者: Mao C;Liu R;Bo L;Chen N;Li S;Xia S;Chen J;Li D;Zhang L;Xu Z
• 通讯作者: Xu Z

Prenatal dehydration alters renin-angiotensin system associated with angiotensin-increased blood pressure in young offspring.

• DOI: 10.1038/hr.2009.155
• 发表时间: 2009-12
• 期刊: HYPERTENSION RESEARCH
• 影响因子: 5.4
• 作者: Guan, Junchang;Mao, Caiping;Xu, Feichao;Geng, Chunsong;Zhu, Liyan;Wang, Aiqing;Xu, Zhice
• 通讯作者: Xu, Zhice

High-salt diet during pregnancy and angiotensin-related cardiac changes.

妊娠期高盐饮食与血管紧张素相关的心脏变化

• DOI: 10.1097/hjh.0b013e328337da8f
• 发表时间: 2010-06
• 期刊: Journal of hypertension
• 影响因子: 4.9
• 作者: Ding Y;Lv J;Mao C;Zhang H;Wang A;Zhu L;Zhu H;Xu Z
• 通讯作者: Xu Z

Changed salt appetite and central angiotensin II-induced cellular activation in rat offspring following hypoxia during fetal stages.

胎儿期缺氧后大鼠后代盐食欲的变化和中枢血管紧张素 II 诱导的细胞激活

• DOI: 10.1016/j.peptides.2010.03.009
• 发表时间: 2010-06
• 期刊: Peptides
• 影响因子: 3
• 作者: Yang W;Mao C;Xia F;Zheng J;Wang A;Zhu L;He R;Xu Z
• 通讯作者: Xu Z

Central angiotensin I increases swallowing activity and oxytocin release in the near-term ovine fetus.

中枢血管紧张素 I 增加近期绵羊胎儿的吞咽活动和催产素释放

• DOI: 10.1159/000332736
• 发表时间: 2012
• 期刊: Neuroendocrinology
• 影响因子: 4.1
• 作者: Shi L;Mao C;Zeng F;Zhang L;Xu Z
• 通讯作者: Xu Z