title: Prenatal cigarette smoke decreases lung cAMP and increases airway hyperresponsiveness.
abstract: Epidemiologic studies suggest that in utero exposure to tobacco smoke, primarily through maternal smoking, increases the risk for asthma in children; however, the mechanism of this phenomenon is not clear. Cyclic adenosine monophosphate relaxes airway smooth muscles in the lung and acts as an antiasthmatic. In this study, we examined the effects of in utero cigarette smoke exposure of Balb/c mice on airway responsiveness, as determined by Penh measurements. Animals exposed prenatally but not postnatally to cigarette smoke exhibited increased airway hyperresponsiveness after a single intratracheal injection of Aspergillus fumigatus extract. The increased airway hyperresponsiveness was not associated with increased leukocyte migration or mucous production in the lung but was causally related to decreased lung cyclic adenosine monophosphate levels, increased phosphodiesterase-4 enzymatic activity, and phosphodiesterase-4D (PDE4D) isoform-specific messenger ribonucleic acid expression in the lung. Exposure of adult mice to cigarette smoke did not significantly alter airway responsiveness, cyclic adenosine monophosphate levels, or the phosphodiesterase activity. These results suggest that prenatal exposure to cigarette smoke affects lung airway reactivity by modulating the lung cyclic adenosine monophosphate levels through changes in phosphodiesterase-4D activity, and these effects are independent of significant mucous production or leukocyte recruitment into the lung.
authors.affiliation: Respiratory Immunology and Asthma Program, Lovelace Respiratory Research Institute, Albuquerque, New Mexico, 87108, USA.
authors.forename: Shashi P
authors.initials: SP
authors.lastname: Singh
authors.forename: Edward G
authors.initials: EG
authors.lastname: Barrett
authors.forename: Roma
authors.initials: R
authors.lastname: Kalra
authors.forename: Seddigheh
authors.initials: S
authors.lastname: Razani-Boroujerdi
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Langley
authors.forename: Viswanath
authors.initials: V
authors.lastname: Kurup
authors.forename: Yohannes
authors.initials: Y
authors.lastname: Tesfaigzi
authors.forename: Mohan L
authors.initials: ML
authors.lastname: Sopori
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000032:analysis; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000209:etiology*; D000242:Cyclic AMP / Q000032:analysis*; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D004195:Disease Models, Animal; D005260:Female; D008168:Lung / Q000737:chemistry*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
chemical_list: D014028:Tobacco Smoke Pollution; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4