Project 3: Role Played by ASIC, P2X and EP4 Receptors in the Exercise Pressor Reflex in Health and Simulated PAD
项目 3:ASIC、P2X 和 EP4 受体在健康和模拟 PAD 运动加压反射中的作用
基本信息
- 批准号:10117112
- 负责人:
- 金额:$ 41.82万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-02-01 至 2023-01-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAnimal Disease ModelsAntioxidantsArrhythmiaArteriesAscorbic AcidAttentionAttenuatedBlood VesselsBlood flowBrainCardiacCardiovascular systemChest PainChronicContractsCoronary arteryDinoprostoneDiseaseEventExerciseFiberGastrocnemius MuscleGoalsHealthHeartHeart ContractilitiesHeart RateHindlimbHourIndividualInfusion proceduresIntermittent ClaudicationIschemiaKidneyLactic acidLightMechanicsMediatingMetabolicMuscleMuscle ContractionMuscle FibersMuscle Form Glycogen PhosphorylaseMyocardialNamesNerveNeuronsOrganOxidative StressOxygenP2X-receptorPainPatientsPatternPeripheralPeripheral arterial diseasePeroxidesPharmacologyPlayPreparationProstaglandinsRattusReflex actionResistanceRoleSignal TransductionSkeletal MuscleSmall Interfering RNASpinal CordSpinal GangliaStimulusSympathetic Nervous SystemTestingThinnessTironTreesTriceps Brachii MuscleVascular blood supplyVascular resistanceVentricular Fibrillationafferent nervearmexperimental studyfemoral arteryknock-downneuromechanismpressurereceptorresponsevasoconstriction
项目摘要
PROJECT SUMMARY/ABSTRACT – PROJECT 3
A reflex arising from the contraction of hindlimb skeletal muscles is an important neural mechanism that is
responsible for the cardiovascular adjustments to exercise. These adjustments, which include increases in
peripheral vascular resistance, cardiac contractility and rate, function to increase arterial blood flow and oxygen
supply to the exercising muscles, and in turn support their ability to contract. This neural mechanism has been
named the exercise pressor reflex and its afferent arm is comprised of group III and IV fibers whose endings
are located in and near the muscle interstitium. In patients with peripheral artery disease (PAD) the exercise
pressor reflex is exaggerated. The overall goal of the experiments proposed in this unit is to shed light on the
metabolic factors occurring in contracting muscles that are responsible for evoking this PAD-induced
exaggeration of the reflex. Metabolic factors produced by contracting skeletal muscles are believed to signal
the spinal cord and brain that the arterial blood supply to working muscle does not meet its metabolic demand.
These metabolites are therefore prime candidates for stimulating the group III and IV afferents responsible for
evoking the exaggerated exercise pressor reflex in PAD. In the proposed experiments, we will pay particular
attention to three important metabolic by-products of contraction, namely Lactic Acid, which stimulates the
ASIC3 channel, Prostaglandin E2, which stimulates the endoperoxide (EP)4 receptor, and ATP which
stimulates the P2X3 receptor. We will examine in decerebrated unanesthetized rats the responses to
contraction of group III and IV muscle afferents both before and during either pharmacological blockade of the
above receptors or after they have been “knocked down” with siRNA. The proposed experiments will also
examine the responses to contraction of these thin fiber afferents before and during knockdown of
myophosphorylase in the triceps surae muscles. The proposed experiments will be performed both in rats with
freely perfused femoral arteries and in rats with femoral arteries that have been ligated for 72 hours before the
start of the experiment. The latter preparation simulates the arterial blood flow patterns seen in patients with
PAD and therefore serves as a useful animal model of this disease. The proposed experiments are anticipated
to provide new information about metabolic factors that cause the exercise pressor reflex to be exaggerated in
PAD.
项目总结/摘要-项目3
由后肢骨骼肌收缩引起的反射是一种重要的神经机制,
负责心血管对运动的调节。这些调整,其中包括增加
外周血管阻力、心脏收缩力和心率、增加动脉血流量和氧气的功能
供应给运动的肌肉,并反过来支持他们的收缩能力。这种神经机制已经被
称为运动加压反射,其传入臂由III和IV组纤维组成,
位于肌筋膜内和附近。在外周动脉疾病(PAD)患者中,
升压反射被放大。本单元提出的实验的总体目标是阐明
发生在收缩肌肉中的代谢因子,负责引起这种PAD诱导的
反射的放大。骨骼肌收缩产生的代谢因子被认为是
脊髓和大脑的动脉血液供应工作肌肉不能满足其代谢需求。
因此,这些代谢物是刺激负责以下功能的III和IV组传入神经的主要候选物:
引起PAD的过度运动升压反射。在拟议的实验中,我们将特别注意
注意收缩的三个重要代谢副产物,即乳酸,它刺激收缩。
ASIC 3通道,前列腺素E2,刺激内过氧化物(EP)4受体,和ATP,
刺激P2 X3受体。我们将在去大脑的未麻醉大鼠中检查对
收缩组III和IV肌肉传入之前和期间,无论是药理学封锁的
或在它们被siRNA“敲低”之后。拟议的实验还将
检查这些细纤维传入的收缩反应之前和期间敲低,
小腿三头肌中的肌磷酸化酶拟进行的实验将在大鼠中进行,
自由灌注的股动脉和股动脉结扎72小时的大鼠,
实验的开始。后一种制剂模拟了在患有以下疾病的患者中观察到的动脉血流模式:
PAD,因此作为这种疾病的一个有用的动物模型。预计拟议的实验
提供了关于代谢因素的新信息,这些代谢因素导致运动加压反射被夸大,
垫.
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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Marc Peter Kaufman其他文献
Marc Peter Kaufman的其他文献
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{{ truncateString('Marc Peter Kaufman', 18)}}的其他基金
Opioid-induced potentiation of the exercise pressor reflex via acid-sensing ion channels (ASIC3) in health and simulated peripheral artery disease
阿片类药物通过酸敏感离子通道 (ASIC3) 在健康和模拟外周动脉疾病中诱导运动升压反射增强
- 批准号:
10593184 - 财政年份:2021
- 资助金额:
$ 41.82万 - 项目类别:
Opioid-induced potentiation of the exercise pressor reflex via acid-sensing ion channels (ASIC3) in health and simulated peripheral artery disease
阿片类药物通过酸敏感离子通道 (ASIC3) 在健康和模拟外周动脉疾病中诱导运动升压反射增强
- 批准号:
10230430 - 财政年份:2021
- 资助金额:
$ 41.82万 - 项目类别:
Opioid-induced potentiation of the exercise pressor reflex via acid-sensing ion channels (ASIC3) in health and simulated peripheral artery disease
阿片类药物通过酸敏感离子通道 (ASIC3) 在健康和模拟外周动脉疾病中诱导运动升压反射增强
- 批准号:
10395569 - 财政年份:2021
- 资助金额:
$ 41.82万 - 项目类别:
Role played by Acid Ion Sensing Channels in Peripheral Artery Disease
酸离子传感通道在外周动脉疾病中的作用
- 批准号:
10531228 - 财政年份:2020
- 资助金额:
$ 41.82万 - 项目类别:
Role played by Acid Ion Sensing Channels in Peripheral Artery Disease
酸离子传感通道在外周动脉疾病中的作用
- 批准号:
10153286 - 财政年份:2020
- 资助金额:
$ 41.82万 - 项目类别:
Role played by Acid Ion Sensing Channels in Peripheral Artery Disease
酸离子传感通道在外周动脉疾病中的作用
- 批准号:
10318665 - 财政年份:2020
- 资助金额:
$ 41.82万 - 项目类别:
Acute and Chronic Afferent Engagement: Sympathetic and End Organ Responses
急性和慢性传入参与:交感神经和终末器官反应
- 批准号:
10117087 - 财政年份:2017
- 资助金额:
$ 41.82万 - 项目类别:
Effects of arterial occlusion on the respon of thin fib. afferents to contraction
动脉闭塞对细纤维反应的影响。
- 批准号:
8001279 - 财政年份:2010
- 资助金额:
$ 41.82万 - 项目类别:
Differential sympathetic reflex control in excerise
运动中交感神经反射的差异控制
- 批准号:
6915186 - 财政年份:2004
- 资助金额:
$ 41.82万 - 项目类别:
Differential sympathetic reflex control in excerise
运动中交感神经反射的差异控制
- 批准号:
7049592 - 财政年份:2004
- 资助金额:
$ 41.82万 - 项目类别:
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