Joad J P, Kott K S, Bric J M
Department of Pediatrics, University of California at Davis, 95616, USA.
Toxicol Appl Pharmacol. 1996 Dec;141(2):561-7. doi: 10.1006/taap.1996.0323.
We studied the local role of C-fibers, in the absence of systemic effects and blood components of inflammation, on lung responses to ozone. Guinea pigs were pretreated with capsaicin to deplete C-fibers or with vehicle. One week later their isolated, buffer-perfused lungs were exposed to 0.8 ppm ozone or air for 2 hr. In some lungs (9 or 10 each group), increasing doses of methacholine followed by capsaicin were injected into the pulmonary artery. In separate lungs (n = 5, each group), lung Substance P content by EIA and NK1 receptor characteristics by radioligand binding were measured. Analyses were performed by two-way ANOVA with a significant interaction indicative of C-fibers playing a role in ozone responses. Ozone increased R(L) and decreased C(dyn), effects which were apparently not dependent on C-fibers. Ozone increased responsiveness to methacholine, an effect which was reduced by depletion of C-fibers. Ozone increased and C-fiber depletion decreased lung responses to capsaicin. C-fiber depletion but not ozone decreased lung substance P content. C-fiber depletion increased the affinity but did not change the number of NK1 receptors, while ozone had no effect. We conclude that the ozone, in the absence of systemic effects and the blood components of inflammation, increased muscarinic reactivity in part via the local effects of C-fibers.
我们研究了在没有全身效应和炎症血液成分的情况下,C纤维对肺部臭氧反应的局部作用。用辣椒素预处理豚鼠以耗尽C纤维,或用赋形剂处理。一周后,将它们分离的、用缓冲液灌注的肺暴露于0.8 ppm臭氧或空气中2小时。在一些肺中(每组9或10个),向肺动脉注射递增剂量的乙酰甲胆碱,随后注射辣椒素。在单独的肺中(每组n = 5),通过酶免疫分析测定肺P物质含量,通过放射性配体结合测定NK1受体特征。采用双向方差分析进行分析,显著的交互作用表明C纤维在臭氧反应中起作用。臭氧增加了肺阻力(R(L))并降低了动态顺应性(C(dyn)),这些效应显然不依赖于C纤维。臭氧增加了对乙酰甲胆碱的反应性,这种效应在C纤维耗尽时会减弱。臭氧增加而C纤维耗尽降低了肺对辣椒素的反应。C纤维耗尽而非臭氧降低了肺P物质含量。C纤维耗尽增加了NK1受体的亲和力,但没有改变其数量,而臭氧没有影响。我们得出结论,在没有全身效应和炎症血液成分的情况下,臭氧部分通过C纤维的局部作用增加了毒蕈碱反应性。