Author(s): Joad JP, Ji C, Kott KS, Bric JM, Pinkerton KE, Joad JP, Ji C, Kott KS, Bric JM, Pinkerton KE
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Abstract We evaluated whether sidestream smoke (SS) exposure in utero and/or postnatally causes airway obstruction and hyperresponsiveness, and whether the effect is associated with neuroendocrine cell hyperplasia. Pregnant Sprague-Dawley rats were exposed to filtered air (FA) or to SS (total suspended particulate concentration, 1.00 +/- 0.07 mg/m3, CO, 4.9 +/- 0.7 ppm; nicotine, 344 +/- 85 micrograms/m3; mean +/- SD) for 4 hr/day, 7 days/week from Day 3 of gestation until birth and then their female pups were exposed to either FA or SS for 7-10 weeks postnatally. This resulted in four exposure conditions: in utero FA followed by postnatal FA (FA/FA), in utero FA followed by postnatal SS (FA/SS), in utero SS followed by postnatal FA (SS/FA), and in utero SS followed by postnatal SS (SS/SS). The lungs from the pups (n = 6-8 of each exposure combination) were then placed in an isolated buffer-perfused system where transpulmonary pressure, airflow, and pulmonary artery pressure (Ppa) were measured while increasing doses of methacholine were injected into the pulmonary artery. Three lungs from each group were then fixed in 1\% paraformaldehyde and neuroendocrine cells were identified immunohistochemically using antibodies to neuron-specific enolase. As compared to lungs from FA/FA-exposed rats, lungs from SS/SS-exposed rats exhibited 24\% lower Cdyn (p = 0.0006, ANOVA), greater reactivity to methacholine (p = 0.0001, repeated measures ANOVA), and more neuroendocrine cells per centimeter basal lamina (p = 0.0006, ANOVA). Lungs from SS/FA- or FA/SS-exposed rats were not different from lungs from FA/FA-exposed rats in any of these parameters. We conclude that exposure to SS both pre- and postnatally (but not only pre- or only postnatally) results in lungs which are less compliant, more reactive to methacholine, and have a greater number of neuroendocrine cells.
This article was published in Toxicol Appl Pharmacol
and referenced in Journal of Environmental & Analytical Toxicology