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29 July 2015 Antenatal Antioxidant Prevents Nicotine-Mediated Hypertensive Response in Rat Adult Offspring
DaLiao Xiao, Xiaohui Huang, Yong Li, Chiranjib Dasgupta, Lei Wang, Lubo Zhang
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Abstract

Previous studies have 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 mini-pumps from Day 4 of gestation to Day 10 after birth, in the absence or presence of the 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 production in offspring, which was abrogated by NAC. Angiotensin II (Ang II)-induced BP responses were significantly higher in nicotine-treated group than in saline-treated control group, and NAC treatment blocked the nicotine-induced increase in BP response. Consistent with that, the nicotine treatment significantly increased both Ang II-induced 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. 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 for increased oxidative stress in nicotine-induced developmental programming of hypertensive phenotype in male offspring.

DaLiao Xiao, Xiaohui Huang, Yong Li, Chiranjib Dasgupta, Lei Wang, and Lubo Zhang "Antenatal Antioxidant Prevents Nicotine-Mediated Hypertensive Response in Rat Adult Offspring," Biology of Reproduction 93(3), (29 July 2015). https://doi.org/10.1095/biolreprod.115.132381
Received: 9 June 2015; Accepted: 1 July 2015; Published: 29 July 2015
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