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Mechanisms of Exercise Pressor Reflex Overactivity in Hypertension

高血压运动升压反射过度活跃的机制

基本信息

批准号：
8257541
负责人：
SCOTT A SMITH
金额：
$ 38.86万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-05-01 至 2015-04-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): In hypertensive individuals, exercise elicits excessive increases in arterial blood pressure, heart rate and vascular resistance. These potentially dangerous elevations in circulatory hemodynamics increase the risk for adverse cardiac events or stroke during exercise. We have previously established that overactivity of the exercise pressor reflex, a circulatory reflex originating within skeletal muscle, contributes importantly to the generation of these heightened cardiovascular responses. Further, evidence from our laboratory suggests that both the muscle mechanoreflex and metaboreflex, the two functional components of the exercise pressor reflex, drive this overactivity. However, the mechanisms underlying exercise pressor reflex dysfunction in hypertension are not clear. Sensory information generated by activation of the exercise pressor reflex is processed within the nucleus tractus solitarius (NTS) of the medulla oblongata. The activity of neurons within the medulla that receive and process this information can be modulated by the endogenous production of nitric oxide (NO). NO production is mediated by nitric oxide synthase (NOS). Likewise, NO activity within the NTS can be modified by the generation of reactive oxygen species (ROS). Therefore, alterations in either NOS expression/activity or ROS production potentially contribute to changes in NO activity within the NTS. As such, the NO pathway within the NTS represents a viable target for disease induced alterations in exercise pressor reflex function. Based on this knowledge, we hypothesize that the enhanced cardiovascular response to exercise mediated by the exercise pressor reflex in hypertension is induced by alterations in NO activity, changes in NOS expression and/or function as well as alterations in the generation of ROS within the NTS. To test these hypotheses, we will perform physiologic and neuro-biochemical studies in normotensive and hypertensive rats to address the following specific aims: 1) determine the role of NO within the NTS in the generation of exercise pressor reflex, mechanoreflex and metaboreflex overactivity in hypertension; 2) determine the role of NOS within the NTS in the generation of exercise pressor reflex, mechanoreflex and metaboreflex overactivity in hypertension; and 3) determine the role of ROS within the NTS in the generation of exercise pressor reflex, mechanoreflex and metaboreflex overactivity in hypertension.

描述（由申请人提供）：在高血压患者中，运动会导致动脉血压、心率和血管阻力过度增加。循环血液动力学的这些潜在危险的升高增加了运动期间不良心脏事件或中风的风险。我们先前已经确定，运动升压反射（一种起源于骨骼肌的循环反射）的过度活动对这些升高的心血管反应的产生有重要贡献。此外，来自我们实验室的证据表明，肌肉机械反射和代谢反射，运动加压反射的两个功能成分，驱动这种过度活动。然而，高血压运动加压反射功能障碍的机制尚不清楚。运动加压反射激活产生的感觉信息在延髓的孤束核（NTS）内处理。接受和处理这些信息的髓质内神经元的活动可以通过内源性一氧化氮（NO）的产生来调节。NO的产生是由一氧化氮合酶（NOS）介导的。同样，NTS内的NO活性可以通过产生活性氧（ROS）来改变。因此，NOS表达/活性或ROS产生的改变可能有助于NTS内NO活性的变化。因此，NTS内的NO通路代表了疾病诱导的运动加压反射功能改变的可行靶点。基于这一认识，我们假设，增强心血管反应的运动介导的运动加压反射高血压是由改变NO活性，NOS的表达和/或功能的变化，以及在NTS内的ROS的产生的改变。为了验证这些假设，我们将在正常血压和高血压大鼠进行生理和神经生化研究，以解决以下具体目标：1）确定在高血压的运动加压反射，机械反射和代谢反射过度活动的产生中，NTS内的NO的作用;（2）确定孤束核内NOS在高血压运动加压反射、机械反射和代谢反射过度活动中的作用;（3）确定NTS内ROS在高血压运动加压反射、机械反射和代谢反射过度活动中的作用。

项目成果

期刊论文数量（14）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The TRPv1 receptor is a mediator of the exercise pressor reflex in rats.

TRPv1 受体是大鼠运动升压反射的介质。

DOI：
10.1113/jphysiol.2009.184952
发表时间：
2010
期刊：
The Journal of physiology
影响因子：
0
作者：
Smith,ScottA;Leal,AnnaK;Williams,MauriceA;Murphy,MeganN;Mitchell,JereH;Garry,MaryG
通讯作者：
Garry,MaryG

Exercise training improves functional sympatholysis in spontaneously hypertensive rats through a nitric oxide-dependent mechanism.