This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Maternal smoking is the major preventable cause of intrauterine growth retardation and prematurity. Perhaps less well appreciated is the recent evidence that smoking during pregnancy leads to decreased lung function, increased respiratory diseases and increased incidence of sudden infant death syndrome (SIDS) in the offspring. Thus it is of major importance to understand the mechanisms underlying smoking-induced changes in the newborn. Our preliminary data suggests that nicotine is one of the factors responsible for the changes in pulmonary function observed in neonates born to smoking mothers. In this project, rhesus monkeys are used to characterize the effects of chronic exposure to low levels of nicotine throughout pregnancy on lung development and function. Preliminary studies demonstrate that exposure of pregnant rhesus monkeys to a nicotine dose consistent with that of smokers alters fetal airway development. Immunohistochemistry shows wide expression of nicotinic receptors in developing lung and nicotine appears to alter the pattern of receptor expression. The purposes of this project are to 1) determine the basis for nicotine's actions by determining the time course and cell specific expression of nicotinic receptor subtype expression in fetal monkey lung; 2) characterize the effect of fetal exposure to nicotine on lung development and function by functional, morphometric, immunohistochemical and molecular analysis; and 3) begin to determine the mechanism underlying nicotine's actions by in vitro studies. From these studies will come the first description of the effects of chronic nicotine exposure on lung function, a determination of the extent to which these effects are reversible, and a beginning understanding of the mechanisms underlying these effects. Definitive knowledge of the effects of nicotine on lung development would provide an important additional tool in smoking control and will lead to new approaches to develop therapies to block the effects of smoking during pregnancy on fetal development.
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