Acute histamine-induced flux of airway liquid: role of neuropeptides.

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.