title: Fetal nicotine exposure increases airway responsiveness and alters airway wall composition in young lambs.
abstract: To test the hypotheses that fetal nicotine exposure alters airway wall composition and enhances the airway response to inhaled methacholine (MCh), lambs were exposed during the last fetal trimester to (1) a low dose (LN) (n=13, 0.5mg/kg/d (maternal weight) of free base nicotine, (2) a moderate dose (MN) (n=10, 1.5mg/kg/d) or (3) saline (n=14). Studies were performed at postnatal days 12, 26 and 52. Prenatal nicotine exposure induced a dose- and age-related hyper-responsiveness to MCh in the proximal airways. Moment analysis of nitrogen decay curves showed no nicotine or MCh effects on ventilation homogeneity or gas-mixing efficiency in the distal airways during MCh inhalations suggesting a bimodal response. Fetal nicotine exposure increased epithelial mucosubstance volume in central (LN, MN) and distal bronchi (LN), increased smooth muscle volume in distal bronchi and bronchioles (LN) and decreased bronchiolar diameter (MN). In conclusion, third trimester nicotine exposure causes hyperreactive proximal airways and alters proximal airway wall composition associated with airflow limitation.
authors.affiliation: Department of Women and Child Health, Göteborg University, SE-416 85 Göteborg, Sweden. kenneth.sandberg@vgregion.se
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Sandberg
authors.forename: Kent E
authors.initials: KE
authors.lastname: Pinkerton
authors.forename: Stanley D
authors.initials: SD
authors.lastname: Poole
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Minton
authors.forename: Håkan W
authors.initials: HW
authors.lastname: Sundell
mesh_terms: D000818:Animals; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000209:etiology*; D001985:Bronchial Provocation Tests; D005260:Female; D005333:Fetus; D008297:Male; D009538:Nicotine / Q000633:toxicity*; D018722:Nicotinic Agonists / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D012123:Pulmonary Ventilation / Q000187:drug effects; D012129:Respiratory Function Tests; D034561:Sheep, Domestic
chemical_list: D018722:Nicotinic Agonists; D009538:Nicotine