Mechanoreflex mediates the exaggerated exercise pressor reflex in heart failure
Mechanoreflex mediates the exaggerated exercise pressor reflex in heart failure
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DOI：
10.1161/circulationaha.105.566745
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发表时间：
2005-10-11
期刊：
影响因子：
37.8
通讯作者：
Garry, MG
中科院分区：
文献类型：
--
作者：
Smith, SA;Mitchell, JH;Garry, MG
背景--在心力衰竭中，运动会引起平均动脉压（MAP）和心率（HR）的过度升高.使用一种新的大鼠模型，我们以前证明，这种夸张的心血管反应是由过度活跃的运动加压反射（EPR）介导的。虽然我们以前确定，在第四组传入神经元群（与反射的代谢成分）的异常启动的夸张的EPR在心力衰竭的发展，这些纤维不介导增强的循环反应的运动。因此，我们假设EPR活性的增强主要是由反射的机械敏感成分介导的（主要由III组传入纤维的激活介导的）。方法和结果-雄性Sprague-Dawley大鼠分为3组：假手术（对照），扩张型心肌病（DCM），和新生儿辣椒素治疗的动物（NNCAP，IV组传入纤维消融）。与假手术组相比，DCM和NNCAP组通过电诱导的后肢静态肌肉收缩激活EPR导致MAP和HR增加更大。在所有组中，在后肢内给予钆（机械敏感受体的选择性阻断剂）减弱了MAP和HR对收缩的反应。然而，这种减少的幅度是更大的DCM和NNCAP与sham animals.Conclusions -从这些数据中，我们得出结论，肌肉机械反射介导的夸张的EPR，在心力衰竭的发展。此外，这些研究结果表明，心力衰竭的机械反射过度活动可能是对IV组纤维功能改变的代偿反应。鉴于这些发现，肌肉机械反射可能作为一个新的目标，在治疗异常循环反应的运动在心力衰竭。
Background - In heart failure, exercise elicits excessive increases in mean arterial pressure (MAP) and heart rate (HR). Using a novel rat model, we previously demonstrated that this exaggerated cardiovascular responsiveness is mediated by an overactive exercise pressor reflex (EPR). Although we previously determined that abnormalities in the group IV afferent neuron population (associated with the metabolic component of the reflex) initiate the development of the exaggerated EPR in heart failure, these fibers do not mediate the enhanced circulatory responses to exercise. Therefore, we hypothesized that the augmentation in EPR activity is primarily mediated by the mechanically sensitive component of the reflex (mediated predominately by activation of group III afferent fibers).Methods and Results - Male Sprague-Dawley rats were divided into 3 groups: sham (control), dilated cardiomyopathic (DCM), and neonatal capsaicin- treated animals (NNCAP, group IV afferent fibers ablated). Activation of the EPR by electrically induced static muscle contraction of the hindlimb resulted in larger increases in MAP and HR in DCM and NNCAP compared with sham animals. In all groups, administration of gadolinium (a selective blocker of mechanically sensitive receptors) within the hindlimb attenuated the MAP and HR responses to contraction. However, the magnitude of this reduction was greater in DCM and NNCAP compared with sham animals.Conclusions - From these data, we conclude that the muscle mechanoreflex mediates the exaggerated EPR that develops in heart failure. Moreover, these findings suggest that mechanoreflex overactivity in heart failure may be a compensatory response to functional alterations in group IV fibers. Given these findings, the muscle mechanoreflex may serve as a novel target in the treatment of the abnormal circulatory responses to exercise in heart failure.