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

• Published in: Brain research Vol. 1243; pp. 47 - 52
• Main Authors: Mao, Caiping, Zhang, Hong, Xiao, Daliao, Zhu, Liyan, Ding, Yang, Zhang, Yuying, Wu, Lei, Xu, Zhice, Zhang, Lubo
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier 03.12.2008
• Subjects: Biological and medical sciences; Medical sciences; Neurology; Tobacco, tobacco smoking; Toxicology; Brain; Fetus; Offspring; AT 1/AT 2 ratio; Nicotine; AT1/AT2 ratio; Rat; Rodentia; Central nervous system; Tobacco smoking; Perinatal; AT1 angiotensin receptor; Encephalon; AT2 angiotensin receptor; Progeny; Vertebrata; Mammalia; Newborn animal; Animal
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2008.09.060

Abstract The present study determined the effect of maternal nicotine exposure during the early developmental period on AT1 R and AT2 R 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 AT1 R in fetuses at gestation 15 and 21 days and decreased central AT2 R at gestation day 21. In the offspring, perinatal nicotine significantly increased brain AT1 R protein in males but not females at 30 days, and increased it in both males and females at 5-month-old. AT2 R protein levels were significantly decreased by nicotine in both male and female offspring regardless of ages. Whereas brain AT1 R mRNA abundance did not change during postnatal development, AT2 R mRNA levels in both sexes significantly decreased in 5-month-old, as compared with 30-day-old offspring. Nicotine significantly increased brain AT1 R mRNA in the female offspring. In contrast, it decreased AT2 R mRNA in the brain to the same extent in males and females. In control offspring, there was a developmental increase in the AT1 R/AT2 R 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 AT1 R and AT2 R gene expression pattern in the developing brain and suggest maternal smoking-mediated pathophysiological consequences related to brain RAS development in postnatal life.