IN-UTERO AND POSTNATAL EFFECTS OF SIDESTREAM CIGARETTE-SMOKE EXPOSURE ON LUNG-FUNCTION, HYPERRESPONSIVENESS, AND NEUROENDOCRINE CELLS IN RATS

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/m(3); CO, 4.9 +/- 0.7 ppm; nicotine, 344 +/- 85 mu g/m(3); 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 (P-pa) 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 C-dyn (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. (C) 1995 Academic Press, Inc.