Haack Karla K V, Zucker Irving H
Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, United States.
Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, United States.
Auton Neurosci. 2015 Mar;188:44-50. doi: 10.1016/j.autneu.2014.10.015. Epub 2014 Oct 18.
The control of sympathetic outflow in the chronic heart failure (CHF) state is markedly abnormal. Patients with heart failure present with increased plasma norepinephrine and increased sympathetic nerve activity. The mechanism for this sympatho-excitation is multiple and varied. Both depression in negative feedback sensory control mechanisms and augmentation of excitatory reflexes contribute to this sympatho-excitation. These include the arterial baroreflex, cardiac reflexes, arterial chemoreflexes and cardiac sympathetic afferent reflexes. In addition, abnormalities in central signaling in autonomic pathways have been implicated in the sympatho-excitatory process in CHF. These mechanisms include increases in central Angiotensin II and the Type 1 receptor, increased in reactive oxygen stress, upregulation in glutamate signaling and NR1 (N-methyl-D-aspartate subtype 1) receptors and others. Exercise training in the CHF state has been shown to reduce sympathetic outflow and result in increased survival and reduced cardiac events. Exercise training has been shown to reduce central Angiotensin II signaling including the Type 1 receptor and reduce oxidative stress by lowering the expression of many of the subunits of NADPH oxidase. In addition, there are profound effects on the central generation of nitric oxide and nitric oxide synthase in sympatho-regulatory areas of the brain. Recent studies have pointed to the balance between Angiotensin Converting Enzyme (ACE) and ACE2, translating into Angiotensin II and Angiotensin 1-7 as important regulators of sympathetic outflow. These enzymes appear to be normalized following exercise training in CHF. Understanding the precise molecular mechanisms by which exercise training is sympatho-inhibitory will uncover new targets for therapy.
慢性心力衰竭（CHF）状态下交感神经输出的控制明显异常。心力衰竭患者表现为血浆去甲肾上腺素增加和交感神经活动增强。这种交感神经兴奋的机制多种多样。负反馈感觉控制机制的抑制和兴奋性反射的增强都促成了这种交感神经兴奋。这些包括动脉压力反射、心脏反射、动脉化学反射和心脏交感传入反射。此外，自主神经通路中的中枢信号异常也与CHF的交感神经兴奋过程有关。这些机制包括中枢血管紧张素II和1型受体增加、活性氧应激增加、谷氨酸信号和NR1（N-甲基-D-天冬氨酸亚型1）受体上调等。CHF状态下的运动训练已被证明可减少交感神经输出，并提高生存率和减少心脏事件。运动训练已被证明可减少包括1型受体在内的中枢血管紧张素II信号，并通过降低NADPH氧化酶许多亚基的表达来减轻氧化应激。此外，运动训练对大脑交感神经调节区域一氧化氮和一氧化氮合酶的中枢生成有深远影响。最近的研究指出，血管紧张素转换酶（ACE）和ACE2之间的平衡转化为血管紧张素II和血管紧张素1-7，是交感神经输出的重要调节因子。在CHF患者中，运动训练后这些酶似乎恢复正常。了解运动训练产生交感神经抑制作用的确切分子机制将为治疗发现新的靶点。
