Sympatho-excitatory response to pulmonary chemosensitive spinal afferent activation in anesthetized, vagotomized rats.
Sympatho-excitatory response to pulmonary chemosensitive spinal afferent activation in anesthetized, vagotomized rats.
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DOI：
10.14814/phy2.13742
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发表时间：
2018-06
影响因子：
2.5
通讯作者：
Wang HJ
中科院分区：
文献类型：
--
作者：
Shanks J;Xia Z;Lisco SJ;Rozanski GJ;Schultz HD;Zucker IH;Wang HJ
众所周知，肺的感觉神经支配由迷走神经和交感神经来源的神经纤维共同完成。尽管肺的迷走神经传入支配已得到充分研究，但对于脊髓交感神经传入纤维介导的生理效应了解较少。我们假设，肺的交感脊髓传入神经纤维的激活会引发兴奋性升压反射，类似于先前在心脏中所描述的那种反射。
在本研究中，我们评估了在麻醉、双侧迷走神经切断的成年Sprague - Dawley大鼠中，通过向肺的脏层胸膜应用激动剂以及向主支气管内给药来激活对TRPV1敏感的肺脊髓感觉纤维后，肾交感神经活动（RSNA）和血流动力学的变化。向肺的脏层胸膜应用缓激肽（BK）可使平均动脉压（MAP）、心率（HR）和RSNA升高。与背侧表面相比，将BK应用于左肺腹侧表面时，这种反应明显更强。相反，将辣椒素（Cap）局部应用于肺的脏层胸膜，会使MAP产生双相反射性变化，同时HR和RSNA增加，这与向心外膜应用Cap时的血流动力学反应非常相似。在肺迷走神经支配完整的动物中，以及通过左主支气管将BK应用于肺的远端气道时，也会引发这种反射。
为了进一步确定这种反射的起源，采用硬膜外应用选择性传入神经毒素（树脂毒素，RTX）来长期损毁T1 - T4背根神经节水平表达TRPV1的胸段传入神经元胞体。在RTX处理9 - 10周后，这种处理消除了迷走神经切断大鼠对心脏和肺部应用BK及Cap所产生的所有交感兴奋反应。这些数据表明存在一种兴奋性肺化学敏感交感传入反射。这一发现可能对诸如肺部炎症和化学刺激物吸入等导致感觉神经激活的肺部疾病具有重要的临床意义。
The sensory innervation of the lung is well known to be innervated by nerve fibers of both vagal and sympathetic origin. Although the vagal afferent innervation of the lung has been well characterized, less is known about physiological effects mediated by spinal sympathetic afferent fibers. We hypothesized that activation of sympathetic spinal afferent nerve fibers of the lung would result in an excitatory pressor reflex, similar to that previously characterized in the heart. In this study, we evaluated changes in renal sympathetic nerve activity (RSNA) and hemodynamics in response to activation of TRPV1‐sensitive pulmonary spinal sensory fibers by agonist application to the visceral pleura of the lung and by administration into the primary bronchus in anesthetized, bilaterally vagotomized, adult Sprague‐Dawley rats. Application of bradykinin (BK) to the visceral pleura of the lung produced an increase in mean arterial pressure (MAP), heart rate (HR), and RSNA. This response was significantly greater when BK was applied to the ventral surface of the left lung compared to the dorsal surface. Conversely, topical application of capsaicin (Cap) onto the visceral pleura of the lung, produced a biphasic reflex change in MAP, coupled with increases in HR and RSNA which was very similar to the hemodynamic response to epicardial application of Cap. This reflex was also evoked in animals with intact pulmonary vagal innervation and when BK was applied to the distal airways of the lung via the left primary bronchus. In order to further confirm the origin of this reflex, epidural application of a selective afferent neurotoxin (resiniferatoxin, RTX) was used to chronically ablate thoracic TRPV1‐expressing afferent soma at the level of T1–T4 dorsal root ganglia pleura. This treatment abolished all sympatho‐excitatory responses to both cardiac and pulmonary application of BK and Cap in vagotomized rats 9–10 weeks post‐RTX. These data suggest the presence of an excitatory pulmonary chemosensitive sympathetic afferent reflex. This finding may have important clinical implications in pulmonary conditions inducing sensory nerve activation such as pulmonary inflammation and inhalation of chemical stimuli.