Am. J. Respir. Crit. Care Med., Volume 164, Number 6, September 2001, 989-994

Prenatal Nicotine Exposure Alters Pulmonary Function in Newborn Rhesus Monkeys

HARMANJATINDER S. SEKHON, JENNIFER A. KELLER, NEAL L. BENOWITZ, and ELIOT R. SPINDEL

Division of Neuroscience, Oregon Regional Primate Research Center, Beaverton, Oregon; Department of Pathology, Oregon Health Sciences University, Portland, Oregon; and Department of Clinical Pharmacology, University of California, San Francisco, San Francisco, California

Epidemiological studies have shown that offspring of women who smoke during pregnancy have abnormal lung function and associated higher incidences of lower respiratory disorders. The recent identification of nicotinic acetylcholine receptors (nAChR) in fetal lung suggests that the direct interaction between nicotine and nAChR in fetal lung may underlie the postnatal pulmonary abnormalities seen in such infants. This hypothesis was tested in monkeys to determine if maternal nicotine exposure would produce changes in lung mechanics in newborn monkeys similar to those observed in human infants whose mothers smoked during pregnancy. Timed pregnant rhesus monkeys were infused with either nicotine (1.5 mg/kg/d, n = 7) or saline (n = 7) using subcutaneous osmotic pumps from Day 26 to 160 of gestation. On Day 160 of pregnancy (term = 165 d), fetuses were delivered by C-section, and the following day were subjected to pulmonary function testing. After testing, animals were sacrificed, and lungs weighed and fixed. Lung weight and fixed lung volume decreased (16% and 14%, respectively) significantly following in utero nicotine exposure. Peak tidal expiratory flow, FEV_0.2, mean mid-expiratory flow, forced expiratory volume at peak expiratory flow (FEV_PEF), and FEV_PEF/FVC% were significantly lower in newborns exposed to nicotine during gestation. Absolute and specific pulmonary resistance increased significantly whereas absolute and specific dynamic compliance remained unchanged in prenatally nicotine-treated pups. These changes in pulmonary function are strikingly similar to the changes observed in offspring of human smokers. This suggests that the interaction of nicotine with nAChR in developing lung is responsible for the altered pulmonary mechanics observed in human infants whose mothers smoked during pregnancy.

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