Sympathetic nerve-dependent regulation of mucosal vascular tone modifies airway smooth muscle reactivity
Sympathetic nerve-dependent regulation of mucosal vascular tone modifies airway smooth muscle reactivity
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DOI：
10.1152/japplphysiol.00632.2010
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发表时间：
2010-11-01
影响因子：
3.3
通讯作者：
Canning, Brendan J.
中科院分区：
文献类型：
--
作者：
Mazzone, Stuart B.;Lim, Lina H. K.;Canning, Brendan J.
气道含有致密的上皮下微血管丛，其参与物质向气道壁的供应和从气道壁的清除。我们着手检验气道平滑肌对支气管收缩剂的反应性可能依赖于气道粘膜血流的假设。免疫组织化学染色确定血管收缩和血管扩张神经纤维与豚鼠气道上皮下血管。麻醉豚鼠气管粘膜微血管的活体显微镜检查显示，阻断α-肾上腺素能受体可使基线小动脉直径增加约40%，而α-肾上腺素能受体激动剂苯肾上腺素可产生超过基线张力的适度（5%）血管收缩。在随后的体内实验中，局部应用组胺引起的气管收缩显著减少（P < 0.05）和增强α-肾上腺素能受体阻滞剂和激活，分别。在致敏动物中，α-肾上腺素能配体对局部施用辣椒素、静脉内施用神经激肽A、吸入组胺和局部施用抗原诱发的气道平滑肌收缩产生相似的显著（P < 0.05）作用。这些反应与α-肾上腺素能配体对气道平滑肌张力的任何直接影响无关。这些数据表明，供应气道的血管中的血流变化通过调节其清除率来调节底层气道平滑肌对局部释放和外源性给药的试剂的反应性。我们推测，粘膜血管功能的变化或气道血管的神经元调节的变化可能有助于气道反应性疾病。
The airways contain a dense subepithelial microvascular plexus that is involved in the supply and clearance of substances to and from the airway wall. We set out to test the hypothesis that airway smooth muscle reactivity to bronchoconstricting agents may be dependent on airway mucosal blood flow. Immunohistochemical staining identified vasoconstrictor and vasodilator nerve fibers associated with subepithelial blood vessels in the guinea pig airways. Intravital microscopy of the tracheal mucosal microvasculature in anesthetized guinea pigs revealed that blockade of alpha-adrenergic receptors increased baseline arteriole diameter by similar to 40%, whereas the alpha-adrenergic receptor agonist phenylephrine produced a modest (5%) vasoconstriction in excess of the baseline tone. In subsequent in vivo experiments, tracheal contractions evoked by topically applied histamine were significantly reduced (P < 0.05) and enhanced by alpha-adrenergic receptor blockade and activation, respectively. alpha-Adrenergic ligands produced similar significant (P < 0.05) effects on airway smooth muscle contractions evoked by topically administered capsaicin, intravenously administered neurokinin A, inhaled histamine, and topically administered antigen in sensitized animals. These responses were independent of any direct effect of alpha-adrenergic ligands on the airway smooth muscle tone. The data suggest that changes in blood flow in the vessels supplying the airways regulate the reactivity of the underlying airway smooth muscle to locally released and exogenously administered agents by regulating their clearance. We speculate that changes in mucosal vascular function or changes in neuronal regulation of the airway vasculature may contribute to airways responsiveness in disease.