Central Osmosensory Mechanisms in Salt-Sensitive Hypertension
盐敏感性高血压的中枢渗透感觉机制
基本信息
- 批准号:8996700
- 负责人:
- 金额:$ 6.79万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2013
- 资助国家:美国
- 起止时间:2013-02-01 至 2016-08-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAnimalsBlood - brain barrier anatomyBlood PressureBrainCardiovascular DiseasesCardiovascular PhysiologyCardiovascular systemCellsControlled StudyDataDevelopmentElectrophysiology (science)ElementsEpithelialEventExcess Dietary SaltGeneticGoalsHealthHormonalHumanHypernatremiaHypertensionHypothalamic structureIn VitroIndiumInfusion proceduresLesionMediatingMembraneMonitorNerveNeural PathwaysNeuraxisNeuronsOsmolalitiesPathogenesisPathway interactionsPeripheral ResistancePlasmaPlayPropertyProsencephalonPublishingRattusResearchReverse Transcriptase Polymerase Chain ReactionRiskRoleSalineSodiumSodium ChannelTestingTimeTranslatingVanilloidWorkbenzamilcapsaicin receptorchannel blockersdietary saltepithelial Na+ channelfeedinghigh salt dietin vivoinnovationnovel therapeuticsorganum vasculosum of the lamina terminalisosmoreceptorparaventricular nucleuspatch clamppreventreceptorresearch studyresponsesalt intakesalt sensitivesalt sensitive hypertensionsmall hairpin RNA
项目摘要
DESCRIPTION (provided by applicant): Excess dietary salt intake is strongly correlated with cardiovascular disease and is regarded as a major contributing factor to the pathogenesis of hypertension. Recent evidence suggests that dietary salt intake acts centrally with other factors to elevate sympathetic nerve activity and arterial blood pressure. Despite recent studies to indicate these effects are mediated by elevations in plasma sodium concentration, the mechanisms by which dietary salt intake or hypernatermia act within the brain to increase sympathetic outflow in salt-sensitive hypertension is not known. Our long-term goal is to identify the neural pathways and cellular mechanism(s) that increase sympathetic nerve activity in salt- sensitive hypertension. The current objective of this application is to identify how changes in dietary salt intake and plasma sodium concentration are sensed by the central nervous system to activate sympathetic circuits to raise arterial blood pressure. The central hypothesis is that increases in plasma sodium concentration activate osmosensitive neurons in the organum vasculosum of the lamina terminalis (OVLT) through transient receptor vanilloid or benzamil-sensitive channels. Subsequent activation of downstream pathways through the hypothalamus and ventrolateral medulla increase sympathetic outflow and blood pressure. We also hypothesize the osmosensory transduction pathways are sensitized in salt-sensitive hypertension. Our rationale for this project is that identification of the cellular elements that mediate the intrinsic osmosensitivity of these neurons and how this translates to changes in arterial blood pressure will provide a framework for the development of novel therapeutic treatments. Supported by strong preliminary data, we will test this hypothesis through 3 specific aims: 1) Aim 1 will identify the cellular elements in OVLT neurons that detect changes in plasma osmolality and subsequently regulate sympathetic outflow and arterial blood pressure, 2) Aim 2 will determine whether the discharge responses, basal firing rates, and membrane properties of OVLT neurons is altered in salt- sensitive hypertension, and 3) Aim 3 will identify the cellular mechanisms within OVLT that increase sympathetic outflow and arterial blood pressure in salt-sensitive hypertension. The approach is innovative because these experiments, for the first time, will identify the cellular element in the central nervous system that detects changes in plasma sodium concentration to regulate sympathetic outflow and arterial blood pressure. The proposed research is significant as these findings will provide a platform for the development of novel therapeutic treatments to target neurons outside the blood brain barrier for the treatment of salt-sensitive hypertension and cardiovascular disease.
描述(由申请人提供):过量的膳食盐摄入与心血管疾病密切相关,被认为是高血压发病机制的主要因素。最近的证据表明,饮食中的盐摄入量与其他因素一起起着中枢作用,以提高交感神经活动和动脉血压。尽管最近的研究表明这些作用是由血浆钠浓度升高介导的,但饮食盐摄入或高钠血症在脑内作用以增加盐敏感性高血压中交感神经流出的机制尚不清楚。我们的长期目标是确定在盐敏感性高血压中增加交感神经活动的神经通路和细胞机制。本申请的当前目的是确定中枢神经系统如何感知饮食盐摄入量和血浆钠浓度的变化以激活交感神经回路来升高动脉血压。中心假设是血浆钠浓度的增加通过瞬时受体香草酸或苯扎明敏感通道激活终板血管器(OVLT)中的神经元。随后通过下丘脑和延髓腹外侧的下游通路的激活增加交感神经流出和血压。我们还假设盐敏感性高血压的感觉传导通路是敏感的。我们这个项目的基本原理是,识别介导这些神经元的内在神经元敏感性的细胞成分,以及这如何转化为动脉血压的变化,将为开发新的治疗方法提供一个框架。在强有力的初步数据的支持下,我们将通过3个具体目标来检验这一假设:1)目的1将鉴定OVLT神经元中检测血浆渗透压的变化并随后调节交感神经流出和动脉血压的细胞元件,2)目的2将确定OVLT神经元的放电响应、基础放电率和膜特性是否在盐敏感性高血压中改变,3)目的3将确定OVLT增加盐敏感性高血压的交感神经流出和动脉血压的细胞机制。这种方法是创新的,因为这些实验将首次确定中枢神经系统中的细胞成分,该细胞成分检测血浆钠浓度的变化以调节交感神经流出和动脉血压。拟议的研究具有重要意义,因为这些发现将为开发新的治疗方法提供平台,以靶向血脑屏障外的神经元,用于治疗盐敏感性高血压和心血管疾病。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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{{ truncateString('SEAN D STOCKER', 18)}}的其他基金
Forebrain electroneutral transporters in salt-sensitive hypertension
盐敏感性高血压中的前脑电中性转运蛋白
- 批准号:
10736529 - 财政年份:2023
- 资助金额:
$ 6.79万 - 项目类别:
Identification of mechano versus chemo-sensitive renal sensory neurons in hypertension
高血压中机械敏感肾感觉神经元与化学敏感肾感觉神经元的鉴定
- 批准号:
10392402 - 财政年份:2020
- 资助金额:
$ 6.79万 - 项目类别:
Identification of mechano versus chemo-sensitive renal sensory neurons in hypertension
高血压中机械敏感肾感觉神经元与化学敏感肾感觉神经元的鉴定
- 批准号:
10593129 - 财政年份:2020
- 资助金额:
$ 6.79万 - 项目类别:
Brain NaCl-sensing in salt-sensitive hypertension.
盐敏感性高血压中的大脑 NaCl 感应。
- 批准号:
9974567 - 财政年份:2019
- 资助金额:
$ 6.79万 - 项目类别:
Brain NaCl-sensing in salt-sensitive hypertension.
盐敏感性高血压中的大脑 NaCl 感应。
- 批准号:
10400857 - 财政年份:2019
- 资助金额:
$ 6.79万 - 项目类别:
Central Osmosensory Mechanisms in Salt-Sensitive Hypertension
盐敏感性高血压的中枢渗透感觉机制
- 批准号:
8606887 - 财政年份:2013
- 资助金额:
$ 6.79万 - 项目类别:
Central Osmosensory Mechanisms in Salt-Sensitive Hypertension
盐敏感性高血压的中枢渗透感觉机制
- 批准号:
9415263 - 财政年份:2013
- 资助金额:
$ 6.79万 - 项目类别:
Central Osmosensory Mechanisms in Salt-Sensitive Hypertension
盐敏感性高血压的中枢渗透感觉机制
- 批准号:
8438620 - 财政年份:2013
- 资助金额:
$ 6.79万 - 项目类别:
Central Osmosensory Mechanisms in Salt-Sensitive Hypertension
盐敏感性高血压的中枢渗透感觉机制
- 批准号:
8793209 - 财政年份:2013
- 资助金额:
$ 6.79万 - 项目类别:
Antihypertensive Effects of Tetanic Baraoreceptor Input Stimulation
强直性压力感受器输入刺激的抗高血压作用
- 批准号:
8011973 - 财政年份:2010
- 资助金额:
$ 6.79万 - 项目类别:
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