Transient in utero nicotine exposure stimulates mechanosensory-dependent lung development

Nicotine receptors are present in the developing lung yet their function is unknown. The transient role of nicotine receptors in lung development has not been addressed. In this study, nicotine's direct effect on smooth muscle contraction, necessary for mechanosensory-dependent fetal lung development, is examined after transient nicotine stimulation to determine the relationship between nicotine exposure, smooth muscle contraction, and fetal lung development. Rat fetuses at 16 days’ gestation were exposed in utero to 5 different concentrations of nicotine or control injected directly into the amniotic fluid. Specific concentrations of in utero nicotine increased the phosphorylated Western blot analysis and immunohistochemistry of muscle contraction proteins. Respiratory function tests on nicotine-exposed rat pups showed a statistically significant decrease in airway resistance earlier in life compared to control and an upward shift of the pressure-volume curve pointing towards a structural maturation of the in utero nicotine-exposed lung. These results are consistent with transient nicotine exposure during intrauterine life stimulating stretch-induced lung organogenesis by altering phosphorylation of muscle contraction proteins. The increase in smooth muscle phosphorylation may stimulate stretch-induced lung organogenesis, which affects lung development and accelerates lung maturation in rats.