title: Gestational exposure of mice to secondhand cigarette smoke causes bronchopulmonary dysplasia blocked by the nicotinic receptor antagonist mecamylamine.
abstract: BACKGROUND
  Cigarette smoke (CS) exposure during gestation may increase the risk of bronchopulmonary dysplasia (BPD)-a developmental lung condition primarily seen in neonates that is characterized by hypoalveolarization, decreased angiogenesis, and diminished surfactant protein production and may increase the risk of chronic obstructive pulmonary disease.
  
  
  OBJECTIVE
  We investigated whether gestational exposure to secondhand CS (SS) induced BPD and sought to ascertain the role of nicotinic acetylcholine receptors (nAChRs) in this response.
  
  
  METHODS
  We exposed BALB/c and C57BL/6 mice to filtered air (control) or SS throughout the gestation period or postnatally up to 10 weeks. Lungs were examined at 7 days, 10 weeks, and 8 months after birth.
  
  
  RESULTS
  Gestational but not postnatal exposure to SS caused a typical BPD-like condition: suppressed angiogenesis [decreased vascular endothelial growth factor (VEGF), VEGF receptor, and CD34/CD31 (hematopoietic progenitor cell marker/endothelial cell marker)], irreversible hypoalveolarization, and significantly decreased levels of Clara cells, Clara cell secretory protein, and surfactant proteins B and C, without affecting airway ciliated cells. Importantly, concomitant exposure to SS and the nAChR antagonist mecamylamine during gestation blocked the development of BPD.
  
  
  CONCLUSIONS
  Gestational exposure to SS irreversibly disrupts lung development leading to a BPD-like condition with hypoalveolarization, decreased angiogenesis, and diminished lung secretory function. Nicotinic receptors are critical in the induction of gestational SS-induced BPD, and the use of nAChR antagonists during pregnancy may block CS-induced BPD.
authors.affiliation: Lovelace Respiratory Research Institute, Albuquerque, New Mexico, USA.
authors.forename: Shashi P
authors.initials: SP
authors.lastname: Singh
authors.forename: Sravanthi
authors.initials: S
authors.lastname: Gundavarapu
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Smith
authors.forename: Hitendra S
authors.initials: HS
authors.lastname: Chand
authors.forename: Ali Imran
authors.initials: AI
authors.lastname: Saeed
authors.forename: Neerad C
authors.initials: NC
authors.lastname: Mishra
authors.forename: Julie
authors.initials: J
authors.lastname: Hutt
authors.forename: Edward G
authors.initials: EG
authors.lastname: Barrett
authors.forename: Matloob
authors.initials: M
authors.lastname: Husain
authors.forename: Kevin S
authors.initials: KS
authors.lastname: Harrod
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Langley
authors.forename: Mohan L
authors.initials: ML
authors.lastname: Sopori
mesh_terms: D000393:Air Pollutants / Q000032:analysis / Q000633:toxicity*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D001997:Bronchopulmonary Dysplasia / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D008168:Lung / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D008464:Mecamylamine / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018733:Nicotinic Antagonists / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D012313:RNA / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D013047:Specific Pathogen-Free Organisms; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
chemical_list: D000393:Air Pollutants; D018733:Nicotinic Antagonists; D014028:Tobacco Smoke Pollution; D012313:RNA; D008464:Mecamylamine