title: Antenatal Antioxidant Prevents Nicotine-Mediated Hypertensive Response in Rat Adult Offspring.
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.
authors.affiliation: Center for Perinatal Biology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, California Dxiao@llu.edu.
authors.forename: DaLiao
authors.initials: D
authors.lastname: Xiao
authors.affiliation: Center for Perinatal Biology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, California.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Huang
authors.affiliation: Center for Perinatal Biology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, California.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.affiliation: Center for Perinatal Biology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, California.
authors.forename: Chiranjib
authors.initials: C
authors.lastname: Dasgupta
authors.affiliation: Center for Perinatal Biology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, California.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Center for Perinatal Biology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, California.
authors.forename: Lubo
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006801:Humans; D006973:Hypertension / Q000139:chemically induced*; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009538:Nicotine / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D018722:Nicotinic Agonists / Q000633:toxicity*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000517:prevention & control; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors
chemical_list: D000975:Antioxidants; D018722:Nicotinic Agonists; D017382:Reactive Oxygen Species; D000804:Angiotensin II; D015240:Phorbol 12,13-Dibutyrate; D009538:Nicotine; D011493:Protein Kinase C; D000111:Acetylcysteine
keywords: antioxidant; blood pressure; perinatal nicotine; programming; vascular dysfunction