Molecular and Cellular Determinants of the Exercise Pressor Reflex in CHF
CHF 运动加压反射的分子和细胞决定因素
基本信息
- 批准号:8573798
- 负责人:
- 金额:$ 44.77万
- 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:2013-08-01 至 2017-07-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAddressAffectAfferent NeuronsAmericanAnimal ExperimentsAnimalsAnti-Inflammatory AgentsAnti-inflammatoryAntioxidantsAreaAttenuatedCardiovascular PhysiologyCardiovascular systemCause of DeathCellsChronicClinical ResearchDataDeteriorationDiseaseEnvironmental air flowExerciseExercise ToleranceFunctional disorderGated Ion ChannelGene TransferGenerationsHeart RateHeart failureHumanHyperventilationImmunofluorescence ImmunologicInflammationLaboratoriesMeasuresMechanicsMediatingMicroinjectionsMitogen-Activated Protein Kinase KinasesMitogen-Activated Protein KinasesModelingModerate ExerciseMolecularMuscleMyocardial InfarctionNerveNeuraxisNeuronsOxidative StressOxygenPathway interactionsPatientsPeripheralPhysical activityPlayProcessQuality of lifeRattusReactive Oxygen SpeciesReflex actionRegulationResearchRestRoleSignal PathwaySkeletal MuscleSodium ChannelSpinal GangliaStressSympathetic Nervous SystemTechniquesTestingTetrodotoxinTimeTrainingUp-RegulationWestern BlottingWorkarmbasecardiovascular risk factorchannel blockerselectrical propertyganglion cellin vivoneuronal cell bodyneuronal excitabilityneuroregulationnovelpatch clamppressurepreventpublic health relevancerelating to nervous systemresearch studyrespiratoryresponsevoltage
项目摘要
DESCRIPTION (provided by applicant): Chronic heart failure (CHF) is one of the leading causes of death in the U.S. A hallmark of CHF patients is elevated sympatho-excitation and exercise intolerance during physical activity. Even during moderate exercise, extreme activation of the sympathetic nervous system is often seen causing an exaggerated pressor response and hyperventilation, which potentially increases cardiovascular risk during physical activity in these
patients. Existing evidence indicates that the exaggerated sympatho-excitation during exercise is directly related to increased contribution of the exercise pressor reflex (EPR). However, the molecular and cellular mechanisms underlying the increased EPR in CHF remain to be determined. Due to underperfused areas of skeletal muscle in CHF, release of reactive oxygen species and inflammation may activate the mitogen-activated protein kinase (MAPK) pathways in muscle afferent neurons. We hypothesize that chronic oxidative stress in muscle afferent terminals initiate activation of the MAPK signaling pathway in muscle afferent neurons in CHF. This activation, in turn, increases the afferent input of the EPR by affecting afferent neuronal excitability. At the cellular level, we hypothesize that enhanced voltage-gated sodium channel (Nav) activity in muscle afferent neurons (DRG's) of CHF rats contributes to the enhanced afferent neuronal excitability and the EPR. Since exercise training (ExT) prevents the exaggerated EPR in a myocardial infarction rat model we propose that ExT prevents the exaggerated EPR, in part, by inhibition of excessive activation of the MAPK pathway. We will use highly integrative techniques including molecular (real-time PCR, single cell real-time PCR, western blot, immunofluorescence, and in vivo gene transfer), cellular (patch clamp) and whole animal experiments (measuring EPR function, single afferent recording) to test these hypotheses. We believe that the proposed research will address important functional and mechanistic issues that directly relate to the quality of life in patients with CHF. Furthermore, w believe that these data will uncover new targets for therapy in CHF.
描述(由申请人提供):慢性心力衰竭(CHF)是美国死亡的主要原因之一,CHF患者的标志是在体育活动期间交感神经兴奋升高和运动不耐受。即使在适度的运动中,交感神经系统的极度激活也经常导致过度的压力反应和过度通气,这可能会增加这些人在体育活动中患心血管疾病的风险
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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Irving H Zucker其他文献
Irving H Zucker的其他文献
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{{ truncateString('Irving H Zucker', 18)}}的其他基金
Molecular and Cellular Determinants of the Exercise Pressor Reflex in CHF
CHF 运动加压反射的分子和细胞决定因素
- 批准号:
9116274 - 财政年份:2013
- 资助金额:
$ 44.77万 - 项目类别:
Molecular and Cellular Determinants of the Exercise Pressor Reflex in CHF
CHF 运动加压反射的分子和细胞决定因素
- 批准号:
8708202 - 财政年份:2013
- 资助金额:
$ 44.77万 - 项目类别:
Molecular and Cellular Determinants of the Exercise Pressor Reflex in CHF
CHF 运动加压反射的分子和细胞决定因素
- 批准号:
8896857 - 财政年份:2013
- 资助金额:
$ 44.77万 - 项目类别:
Support for the recruit of a tenure track faculty member, Lie Gao, M.D., Ph.D.
支持聘任终身教职人员高烈(Lie Gau)医学博士、博士。
- 批准号:
7860787 - 财政年份:2009
- 资助金额:
$ 44.77万 - 项目类别:
Support for the recruit of a tenure track faculty member, Lie Gao, M.D., Ph.D.
支持聘任终身教职人员高烈(Lie Gau)医学博士、博士。
- 批准号:
7995955 - 财政年份:2009
- 资助金额:
$ 44.77万 - 项目类别:
Regulation of Central AT1R Expression in Heart Failure and Modulation by Exercise
心力衰竭中中枢 AT1R 表达的调节和运动的调节
- 批准号:
7750832 - 财政年份:2009
- 资助金额:
$ 44.77万 - 项目类别:
SYMPATHETIC OUTFLOW IN HEART FAILURE: ANG II, NO AND ROS
心力衰竭中的交感神经流出:ANG II、NO 和 ROS
- 批准号:
6928281 - 财政年份:2004
- 资助金额:
$ 44.77万 - 项目类别:
SYMPATHETIC OUTFLOW IN HEART FAILURE--ANGIOTENSIN II AND NITRIC OXIDE
心力衰竭中的交感神经流出——血管紧张素 II 和一氧化氮
- 批准号:
6606555 - 财政年份:2002
- 资助金额:
$ 44.77万 - 项目类别:
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