ENDOTHELIN CONTROL OF RENAL HEMODYNAMIC AND EXCRETORY FUNCTION
ENDOTHELIN CONTROL OF RENAL HEMODYNAMIC AND EXCRETORY FUNCTION
批准号:
8661220
负责人:
DAVID M POLLOCK
金额:
$219.9万
依托单位国家:
美国
项目类别:
财政年份:
2010
资助国家:
美国
项目状态:
已结题
起止时间:
2010-08-06 至 2016-04-30
关键词:
Angiotensin IIAnimal ModelAnimalsBasic ScienceBlood PressureChronicClinical TrialsDefectDevelopmentDiabetic NephropathyDietDiseaseDuct (organ) structureEndothelinEndothelin A ReceptorEndothelin ReceptorEndothelin-1EndotheliumEquilibriumExcretory functionFutureGene ExpressionGenesGeneticGoalsHealthHumanHypertensionInflammationInflammatoryInfusion proceduresInvestigationKidneyKidney DiseasesMalignant HypertensionMarketingMeasuresMicrocirculationMitogen-Activated Protein KinasesModelingNatureOrganOxidative StressOxidative Stress PathwayPathway interactionsPatientsPeripheral NervesPharmaceutical PreparationsPhasePhysiologicalPlayPopulationProductionPulmonary HypertensionRefractoryRenal functionRenin-Angiotensin SystemResearchResearch PersonnelRoleSeriesSignal TransductionSodiumSodium ChlorideSystemTissuesTubular formationVascular Smooth MuscleVasoconstrictor AgentsVasodilationWorkautocrinebaseblood pressure regulationclinically relevanteffective therapyendothelial dysfunctionhemodynamicshypertension treatmentinhibitor/antagonistinsightnovel therapeutic interventionparacrineprogramsreceptorreceptor functionsalt sensitive hypertensionsignal processingvasoconstriction
中文摘要
盐敏感性或盐依赖性血压升高在大多数人群中是明显的。控制钠排泄的肾缺陷是导致盐依赖性高血压的主要原因。每位项目负责人在过去10年的工作提供了关于肾内皮素(ET- 1)系统在控制钠排泄、肾脏血流动力学和血压方面的强大作用的重要信息,表明内皮素系统在生理意义上可与肾素-血管紧张素系统相媲美。这包括重要的证据表明,高盐饮食,即使没有高血压,对肾脏血流动力学功能有显著影响。我们的研究使我们假设,ETB受体的功能是对ETA受体强大的血管收缩和高血压作用的一种平衡。然而,关于决定这些受体系统活性的具体条件,根本没有足够的信息。目前的建议是基于研究表明,ETA受体在促进高血压和相关的终末器官损伤中起作用,而缺乏ETB受体功能会导致对盐诱导高血压的敏感性增加。因此,当前项目的目标是通过从基因水平到全动物模型的一系列实验方法来确定ET-1的生理作用,以全面探索肾脏中调节ET-1活性的途径。
英文摘要
Salt-sensitivity or salt-dependent elevations in blood pressure are evident in a majority of the human population. Renal defects in the control of sodium excretion are known to be major contributors to the development of salt-dependent hypertension. Work conducted by each of the Project Leaders over the past 10 years has provided important Information about the powerful role of the renal endothelin (ET- 1) system in the control of sodium excretion, renal hemodynamics, and blood pressure indicating that the endothelin system rivals the renin-angiotensin system in physiological significance. This includes important evidence that a high salt diet, even without hypertension, has a significant influence on renal hemodynamic function. Our studies have led us to hypothesize that the ETB receptor functions as a counter-balance to the powerful vasoconstrictor and pro-hypertensive actions of the ETA receptor. However, there is simply not enough information available about the specific conditions that determine the activity of these receptor systems. The current proposal builds on studies demonstrating that the ETA receptor plays a role in promoting hypertension and associated end-organ damage while a lack of ETB receptor function results in increased sensitivity to salt-induced hypertension. Therefore, the goal of the current Program Project is to determine the physiological actions of ET-1 using an array of experimental approaches ranging from the gene level to whole animal models to comprehensively explore the pathways regulating ET-1 activity in the kidney.
The current Program is made of four Projects. Each project explores a unique aspect of the endothelin system in terms of both hemodynamics and tubular function and will elucidate the receptor subtype specific actions on inflammation, oxidative stress, renal hemodynamics and tubular function; a particular emphasis is on factors that influence the control of sodium excretion and blood pressure. These studies are expected to provide important new insight into a major system that regulates renal sodium excretion. In particular, this Program will investigate a full range of mechanisms that control ET-1 release and receptor specific actions in order to provide clinically relevant information.
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DOI:
10.1152/ajprenal.00639.2016
发表时间:
2017-02
期刊:
American journal of physiology. Renal physiology
影响因子:
--
作者:
[Eman Y. Gohar;M. Kasztan;D. Pollock]
通讯作者:
Eman Y. Gohar;M. Kasztan;D. Pollock
DOI:
10.1038/ki.2014.143
发表时间:
2014-11
期刊:
Kidney international
影响因子:
19.6
作者:
[]
通讯作者:
DOI:
10.1016/j.lfs.2015.10.037
发表时间:
2016-08-15
期刊:
Life sciences
影响因子:
6.1
作者:
[Pandit MM, Gao Y, van Hoek A, Kohan DE]
通讯作者:
Kohan DE
Introduction: basic biology of the renal endothelin system.
简介:肾内皮素系统的基础生物学。
DOI:
10.1016/j.semnephrol.2015.02.001
发表时间:
2015
期刊:
Seminars in nephrology
影响因子:
3.3
作者:
[Kohan,DonaldE]
通讯作者:
Kohan,DonaldE
Na delivery and ENaC mediate flow regulation of collecting duct endothelin-1 production.
Na 输送和 ENaC 介导集合管内皮素 1 产生的流量调节。
DOI:
10.1152/ajprenal.00034.2012
发表时间:
2012
期刊:
American journal of physiology. Renal physiology
影响因子:
--
作者:
[Pandit,MeghanaM, Strait,KevinA, Matsuda,Toshio, Kohan,DonaldE]
通讯作者:
Kohan,DonaldE
共 6 条
Cardiovascular Phenotyping Core B
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批准号:10555123
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Deep South KUH Premier Research - Interdisciplinary Mentored Education (PRIME) Training Core
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Integrating novel mechanisms controlling sodium excretion and blood pressure
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FASEB SRC on Renal Hemodynamics: Integrating with the nephron and beyond
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ENDOTHELIN CONTROL OF RENAL HEMODYNAMIC AND EXCRETORY FUNCTION
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资助金额:$18.62万
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Renal endothelin receptor-specific function in angiotensin ll-dependent hypertens
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资助金额:$32.02万
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Endothelial Receptor Action in Na-Dependent Hypertension
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PRE-DOCTORAL TRAINING IN CARDIOVASCULAR BIOLOGY
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海外基金