Perinatal exposure to aged and diluted sidestream cigarette smoke producesairway hyperresponsiveness in older rats

Exposing rats to aged and diluted sidestream cigarette smoke (ADSS) through out in utero and postnatal life results in airway hyperresponsiveness and a n increase in pulmonary neuroendocrine cells (PNECs) and neuroepithelial bo dies (NEBs) in 7- to 10-week-old rats. Since human epidemiologic studies su ggest that perinatal exposure to environmental tobacco smoke (ETS) may be d etrimental to the lung function of older children, this study was designed to determine if perinatal exposure alone results in airway hyperresponsiven ess and increased PNECs/NEBs later in life in rats. Pregnant Sprague-Dawley rats were exposed to filtered air (FA, n = 7) or ADSS (1 mg/m(3) total sus pended particulates, n = 7) for 4 to 6 h/day starting on Day 3 of gestation , Their pups continued to receive the same exposure regimen postnatally unt il 21 days of age. Thereafter all pups were exposed to FA until about 8 wee ks of age. The airway responsiveness of one female pup from each litter was then assessed using an isolated perfused lung system whereby increasing do ses of methacholine (-9.25 to -7.50 log mel) were administered into the pul monary artery and lung resistance (RL), dynamic compliance (Cdyn), and pulm onary pressure (Ppa) were measured. The number of PNECs/NEBs and mast cells per millimeter basal lamina were determined using immunocytochemical and h istological staining and morphometric analysis. Statistics were performed u sing an unpaired Student's t test and repeated measures analysis of varianc e, Perinatal ADSS exposure enhanced methacholine-induced changes in RL CP 0 .02), Cdyn (p = 0.004), and Ppa (p = 0.007). At the highest dose of methach oline, RL in the ADSS-exposed lungs was threefold that in FA-exposed lungs. Although total PNEC number increased approximately twofold in the ADSS-exp osed animals, this change was not found to be statistically significant. Ma st cell number also was not different between groups. These data suggest th at exposure to ADSS during the perinatal period followed by 5 weeks exposur e to FA induces airway hyperresponsiveness in the absence of a significant change in PNECs, NEBs, or mast cells. (C) 1999 Academic Press.