Abstract

We established a guinea pig model to investigate effects of in utero and neonatal exposure to sidestream cigarette smoke (SSCS) on bronchial reactivity during early life. Animals were divided into four groups: 1) room air/room air, 2) sham/sham, 3) SSCS/room air, and 4) SSCS/SSCS. Pregnant and neonatal animals of group 1 breathed room air and those of group 2 were sham treated. Pregnant animals of both groups 3 and 4 as well as neonates of group 4 were exposed to SSCS. SSCS exposure was limited to between days 28 and 55 of pregnancy and days 8 and 24 of the neonatal period. Bronchial response to acetylcholine (ACh) and substance P (SP) were determined in very young animals at 25 days of age. Maximal expiratory flow was used as an index of airway dimension. SP, but not ACh, induced a significantly larger decrease in peak maximal expiratory flow in group 4, indicating an important role of neonatal SSCS exposure in augmenting bronchial response to SP. To further investigate the role of tachykinins in cigarette smoke-induced changes in bronchial reactivity, four additional groups (the same as above) of neonates were pretreated with capsaicin to deplete tachykinins. In the SSCS/SSCS group, SP-induced airway hyperreactivity was abolished by capsaicin pretreatment. Furthermore, in all four groups, capsaicin pretreatment abolished the bronchial response to SP but not the response to ACh. In additional very young animals, acute SSCS caused a nonsignificant increase in bronchial response to SP. These results indicate that chronic neonatal SSCS exposure induces bronchial hyperreactivity to SP; this hyperreactivity is abolished by capsaicin pretreatment.

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