Machhada Asif, Marina Nephtali, Korsak Alla, Stuckey Daniel J, Lythgoe Mark F, Gourine Alexander V
Centre for Cardiovascular and Metabolic Neuroscience, Neuroscience, Physiology and Pharmacology, University College London, London, WC1E 6BT, UK.
UCL Centre for Advanced Biomedical Imaging, Division of Medicine, University College London, London, WC1E 6DD, UK.
J Physiol. 2016 Jul 15;594(14):4017-30. doi: 10.1113/JP270984. Epub 2016 Apr 28.
The strength, functional significance and origins of parasympathetic innervation of the left ventricle remain controversial. This study tested the hypothesis that parasympathetic control of left ventricular contractility is provided by vagal preganglionic neurones of the dorsal motor nucleus (DVMN). Under β-adrenoceptor blockade combined with spinal cord (C1) transection (to remove sympathetic influences), systemic administration of atropine increased left ventricular contractility in rats anaesthetized with urethane, confirming the existence of a tonic inhibitory muscarinic influence on cardiac inotropy. Increased left ventricular contractility in anaesthetized rats was observed when DVMN neurones were silenced. Functional neuroanatomical mapping revealed that vagal preganglionic neurones that have an impact on left ventricular contractility are located in the caudal region of the left DVMN. These neurones provide functionally significant parasympathetic control of left ventricular inotropy.
The strength, functional significance and origins of direct parasympathetic innervation of the left ventricle (LV) remain controversial. In the present study we used an anaesthetized rat model to first confirm the presence of tonic inhibitory vagal influence on LV inotropy. Using genetic neuronal targeting and functional neuroanatomical mapping we tested the hypothesis that parasympathetic control of LV contractility is provided by vagal preganglionic neurones located in the dorsal motor nucleus (DVMN). It was found that under systemic β-adrenoceptor blockade (atenolol) combined with spinal cord (C1) transection (to remove sympathetic influences), intravenous administration of atropine increases LV contractility in rats anaesthetized with urethane, but not in animals anaesthetized with pentobarbital. Increased LV contractility in rats anaesthetized with urethane was also observed when DVMN neurones targeted bilaterally to express an inhibitory Drosophila allatostatin receptor were silenced by application of an insect peptide allatostatin. Microinjections of glutamate and muscimol to activate or inhibit neuronal cell bodies in distinct locations along the rostro-caudal extent of the left and right DVMN revealed that vagal preganglionic neurones, which have an impact on LV contractility, are located in the caudal region of the left DVMN. Changes in LV contractility were only observed when this subpopulation of DVMN neurones was activated or inhibited. These data confirm the existence of a tonic inhibitory muscarinic influence on LV contractility. Activity of a subpopulation of DVMN neurones provides functionally significant parasympathetic control of LV contractile function.
左心室副交感神经支配的强度、功能意义及起源仍存在争议。本研究检验了如下假设：左心室收缩性的副交感神经控制由迷走神经背核（DVMN）的迷走神经节前神经元提供。在β肾上腺素能受体阻断联合脊髓（C1）横断（以消除交感神经影响）的情况下，对用乌拉坦麻醉的大鼠进行全身阿托品给药，可增强左心室收缩性，证实了对心肌收缩力存在一种持续性抑制性毒蕈碱作用。当DVMN神经元沉默时，观察到麻醉大鼠的左心室收缩性增强。功能神经解剖图谱显示，对左心室收缩性有影响的迷走神经节前神经元位于左DVMN的尾侧区域。这些神经元对左心室收缩性提供了具有功能意义的副交感神经控制。
左心室（LV）直接副交感神经支配的强度、功能意义及起源仍存在争议。在本研究中，我们使用麻醉大鼠模型首先证实了迷走神经对LV收缩力存在持续性抑制作用。通过基因神经元靶向和功能神经解剖图谱，我们检验了如下假设：LV收缩性的副交感神经控制由位于迷走神经背核（DVMN）的迷走神经节前神经元提供。结果发现，在全身β肾上腺素能受体阻断（阿替洛尔）联合脊髓（C1）横断（以消除交感神经影响）的情况下，对用乌拉坦麻醉的大鼠静脉注射阿托品可增强左心室收缩性，但对用戊巴比妥麻醉的动物则无此作用。当双侧靶向表达抑制性果蝇咽侧体抑制素受体的DVMN神经元通过应用昆虫肽咽侧体抑制素使其沉默时，也观察到用乌拉坦麻醉的大鼠左心室收缩性增强。向左右DVMN沿头-尾范围的不同位置微量注射谷氨酸和蝇蕈醇以激活或抑制神经元胞体，结果显示，对LV收缩性有影响的迷走神经节前神经元位于左DVMN的尾侧区域。仅当这一DVMN神经元亚群被激活或抑制时，才观察到LV收缩性的变化。这些数据证实了对LV收缩力存在一种持续性抑制性毒蕈碱作用。DVMN神经元亚群的活动对LV收缩功能提供了具有功能意义的副交感神经控制。
