Tobacco-Related Disease Research Program
Antenatal Antioxidant Prevents Nicotine-Mediated Hypertensive Response in Rat Adult Offspring.
- Author(s): Xiao, DaLiao
- Huang, Xiaohui
- Li, Yong
- Dasgupta, Chiranjib
- Wang, Lei
- Zhang, Lubo
- et al.
Published Web Locationhttp://www.ncbi.nlm.nih.gov/pubmed/26224008
Previous studies demonstrated that perinatal nicotine exposure increased blood pressure (BP) in adult offspring. However, the underlying mechanisms were unclear. The present study tested the hypothesis that perinatal nicotine-induced programming of hypertensive response is mediated by enhanced reactive oxygen species (ROS) in the vasculature. Nicotine was administered to pregnant rats via subcutaneous osmotic minipumps from Day 4 of gestation to Day 10 after birth, in the absence or presence of a ROS inhibitor, N-acetyl-cysteine (NAC) in the drinking water. Experiments were conducted in 8-mo-old male offspring. Perinatal nicotine treatment resulted in a significant increase in arterial ROS productions in offspring, which was abrogated by NAC. Angiotensin II (Ang II)-induced BP responses were significantly higher in nicotine-treated group than in saline control group, and NAC treatment blocked the nicotine-induced increase in BP response. In consistence, the nicotine treatment significantly increased both Ang II- and phorbol [12, 13]-dibutyrate (PDBu, a Prkc activator)-induced arterial contractions in adult offspring, which were blocked by NAC treatment. In addition, perinatal nicotine treatment significantly attenuated acetylcholine-induced arterial relaxation in offspring, which was also inhibited by NAC treatment. The results demonstrate that inhibition of ROS blocks the nicotine-induced increase in arterial reactivity and BP response to vasoconstrictors in adult offspring, suggesting a key role of increased oxidative stress in nicotine-induced developmental programming of hypertensive phenotype in male offspring.