Burdon Sanderson Cardiac Science Centre, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.
Am J Physiol Regul Integr Comp Physiol. 2013 Dec 15;305(12):R1411-20. doi: 10.1152/ajpregu.00118.2013. Epub 2013 Sep 4.
High levels of sympathetic drive in several cardiovascular diseases including postmyocardial infarction, chronic congestive heart failure and hypertension are reinforced through dysregulation of afferent input and central integration of autonomic balance. However, recent evidence suggests that a significant component of sympathetic hyperactivity may also reside peripherally at the level of the postganglionic neuron. This has been studied in depth using the spontaneously hypertensive rat, an animal model of genetic essential hypertension, where larger neuronal calcium transients, increased release and impaired reuptake of norepinephrine in neurons of the stellate ganglia lead to a significant tachycardia even before hypertension has developed. The release of additional sympathetic cotransmitters during high levels of sympathetic drive can also have deleterious consequences for peripheral cardiac parasympathetic neurotransmission even in the presence of β-adrenergic blockade. Stimulation of the cardiac vagus reduces heart rate, lowers myocardial oxygen demand, improves coronary blood flow, and independently raises ventricular fibrillation threshold. Recent data demonstrates a direct action of the sympathetic cotransmitters neuropeptide Y (NPY) and galanin on the ability of the vagus to release acetylcholine and control heart rate. Moreover, there is as a strong correlation between plasma NPY levels and coronary microvascular function in patients with ST-elevation myocardial infarction being treated with primary percutaneous coronary intervention. Antagonists of the NPY receptors Y1 and Y2 may be therapeutically beneficial both acutely during myocardial infarction and also during chronic heart failure and hypertension. Such medications would be expected to act synergistically with β-blockers and implantable vagus nerve stimulators to improve patient outcome.
在包括心肌梗死后、慢性充血性心力衰竭和高血压在内的几种心血管疾病中，交感神经驱动的高水平通过传入输入的失调和自主平衡的中枢整合得到加强。然而，最近的证据表明，交感神经活性的一个重要组成部分也可能存在于节后神经元的外周水平。这在自发性高血压大鼠中进行了深入研究，这是一种遗传性高血压的动物模型，其中星状神经节神经元中的钙瞬变增大、去甲肾上腺素释放增加和再摄取受损导致显著的心动过速，甚至在高血压发展之前。在高水平的交感神经驱动下，额外的交感神经递质的释放也会对周围心脏副交感神经传递产生有害影响，即使存在β-肾上腺素能阻断。刺激心脏迷走神经可降低心率、降低心肌耗氧量、改善冠状动脉血流，并独立提高心室颤动阈值。最近的数据表明，交感神经递质神经肽 Y（NPY）和甘丙肽对迷走神经释放乙酰胆碱和控制心率的能力具有直接作用。此外，在接受直接经皮冠状动脉介入治疗的 ST 段抬高型心肌梗死患者中，血浆 NPY 水平与冠状动脉微血管功能之间存在很强的相关性。NPY 受体 Y1 和 Y2 的拮抗剂在心肌梗死后急性期以及慢性心力衰竭和高血压期间可能具有治疗益处。此类药物预计将与β受体阻滞剂和可植入的迷走神经刺激器协同作用，以改善患者的预后。
