Perinatal nicotine exposure alters AT1 and AT2 receptor expression pattern in the brain of fetal and offspring rats

The present study determined the effect of maternal nicotine exposure during the early developmental period on AT1R and AT2R mRNA and protein abundance in the rat brain. Pregnant rats of day-4 gestation were implanted with osmotic minipumps that delivered nicotine at a dose rate of 6 mg/kg/day for 28 days. Neither fetal nor offspring brain weight was significantly altered by the nicotine treatment. Nicotine significantly increased brain AT1R in fetuses at gestation 15 and 21 days and decreased central AT2R at gestation day 21. In the offspring, perinatal nicotine significantly increased brain AT1R protein in males but not females at 30 days, and increased it in both males and females at 5-month-old. AT2R protein levels were significantly decreased by nicotine in both male and female offspring regardless of ages. Whereas brain AT1R mRNA abundance did not change during postnatal development, AT2R mRNA levels in both sexes significantly decreased in 5-month-old, as compared with 30-day-old offspring. Nicotine significantly increased brain AT1R mRNA in the female offspring. In contrast, it decreased AT2R mRNA in the brain to the same extent in males and females. In control offspring, there was a developmental increase in the AT1R/AT2R mRNA ratio in the brain of adult animals, which was significantly up-regulated in nicotine-treated animals with females being more prominent than males. The results demonstrate that perinatal nicotine exposure alters AT1R and AT2R gene expression pattern in the developing brain and suggest maternal smoking-mediated pathophysiological consequences related to brain RAS development in postnatal life.