Yager D, Martins M A, Feldman H, Kamm R D, Drazen J M
Department of Environmental Science and Physiology, Harvard School of Public Health, Boston, Massachusetts, USA.
J Appl Physiol (1985). 1996 Apr;80(4):1285-95. doi: 10.1152/jappl.1996.80.4.1285.
The role of capsaicin-sensitive neuropeptides in the accumulation of airway wall liquid observed 30 s after histamine infusion was investigated in guinea pigs. Two groups were studied: normal animals and animals in which endogenous neuropeptides had been depleted by capsaicin pretreatment. A rapid intravenous infusion of saline or histamine (11 micrograms/kg resulted in marked but similar changes in pulmonary mechanics in normal and capsaicin-pretreated animals. To assess liquid accumulation in airway wall compartments, the lungs were frozen 30 s after histamine infusion; airways from these lungs, 0.15-2.44 mm in internal perimeter, were imaged by low-temperature scanning electron microscopy. There was no difference in average airway surface liquid thickness (hASL) in normal or capsaicin-pretreated airways in response to saline. In capsaicin-pretreated animals, histamine infusion was associated with a significantly decreased hASL (hASL, cap11/hASL,cap0 = 0.58, P < 0.04). Capsaicin pretreatment, without histamine exposure, caused significant increases in epithelial and submucosal areas (Aepi,cap0/Aepi,norm0 = 1.23, P < 0.06; Asub,cap0/Asub,norm0 = 1.40, P < 0.01). The notation cap0 and cap11 indicates capsaicin-pretreated airways given 0 or 11 micrograms/kg histamine, respectively; similarly, norm0 and norm11 indicate normal airways given 0 and 11 micrograms/kg histamine, respectively. Histamine infusion in capsaicin-pretreated animals was associated with liquid shifts from epithelium to lamina propria and from submucosa to adventitia; however, the total wall area was similar to, if not smaller than, that in capsaicin-pretreated animals without histamine treatment. In contrast, histamine infusion in normal animals resulted in significant increases in the areas of the epithelial and lamina propria compartments (Aepi,norm11/Aepi,norm0 = 1.25, P < 0.05; Alp,norm11/Alp,norm0 = 2.19, P < 0.001) as well as a substantial increase in adventitial area, which was significantly attenuated by capsaicin pretreatment (Aadv,cap11/Aadv,norm11 = 0.40, P < 0.001). The resulting total wall area was more than twice that in normal animals without histamine treatment. Our data indicate that histamine-induced accumulation of liquid in the epithelium, lamina propria, and adventitia of normal airways is rapid in onset, most likely derives from a leaky bronchial microvasculature, and is mediated by the secondary release of neurokinins.
在豚鼠中，研究了辣椒素敏感神经肽在组胺输注30秒后观察到的气道壁液体蓄积中的作用。研究了两组：正常动物和经辣椒素预处理使内源性神经肽耗竭的动物。快速静脉输注生理盐水或组胺（11微克/千克）导致正常动物和经辣椒素预处理的动物的肺力学发生明显但相似的变化。为了评估气道壁各层中的液体蓄积情况，在组胺输注30秒后将肺冷冻；对这些肺中内径为0.15 - 2.44毫米的气道进行低温扫描电子显微镜成像。在正常或经辣椒素预处理的气道中，生理盐水处理后的平均气道表面液体厚度（hASL）没有差异。在经辣椒素预处理的动物中，组胺输注与hASL显著降低相关（hASL，cap11/hASL，cap0 = 0.58，P < 0.04）。未经组胺暴露的辣椒素预处理导致上皮和黏膜下层面积显著增加（Aepi，cap0/Aepi，norm0 = 1.23，P < 0.06；Asub，cap0/Asub，norm0 = 1.40，P < 0.01）。符号cap0和cap11分别表示给予0或11微克/千克组胺的经辣椒素预处理的气道；类似地，norm0和norm11分别表示给予0和11微克/千克组胺的正常气道。在经辣椒素预处理的动物中，组胺输注与液体从上皮转移到固有层以及从黏膜下层转移到外膜有关；然而，总壁面积与未经组胺处理的经辣椒素预处理的动物相似，甚至可能更小。相比之下，正常动物中的组胺输注导致上皮和固有层区域面积显著增加（Aepi，norm11/Aepi，norm0 = 1.25，P < 0.05；Alp，norm11/Alp，norm0 = 2.19，P < 0.001）以及外膜面积大幅增加，而辣椒素预处理可显著减轻这种增加（Aadv，cap11/Aadv，norm11 = 0.40，P < 0.001）。由此产生的总壁面积是未经组胺处理的正常动物的两倍多。我们的数据表明，组胺诱导的正常气道上皮、固有层和外膜中液体的蓄积起病迅速，很可能源于支气管微血管渗漏，并由神经激肽的二次释放介导。
