title: Protective Effect of Antenatal Antioxidant on Nicotine-Induced Heart Ischemia-Sensitive Phenotype in Rat Offspring.
abstract: Fetal nicotine exposure increased risk of developing cardiovascular disease later in life. The present study tested the hypothesis that perinatal nicotine-induced programming of heart ischemia-sensitive phenotype is mediated by enhanced reactive oxygen species (ROS) in offspring. 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 drinking water. Experiments were conducted in 8 month old age male offspring. Isolated hearts were perfused in a Langendorff preparation. Perinatal nicotine treatment significantly increased ischemia and reperfusion-induced left ventricular injury, and decreased post-ischemic recovery of left ventricular function and coronary flow rate. In addition, nicotine enhanced cardiac ROS production and significantly attenuated protein kinase Cε (PKCε) protein abundance in the heart. Although nicotine had no effect on total cardiac glycogen synthase kinase-3β (GSK3β) protein expression, it significantly increased the phosphorylation of GSK3β at serine 9 residue in the heart. NAC inhibited nicotine-mediated increase in ROS production, recovered PKCε gene expression and abrogated increased phosphorylation of GSK3β. Of importance, NAC blocked perinatal nicotine-induced increase in ischemia and reperfusion injury in the heart. These findings provide novel evidence that increased oxidative stress plays a causal role in perinatal nicotine-induced developmental programming of ischemic sensitive phenotype in the heart, and suggest potential therapeutic targets of anti-oxidative stress in the treatment of ischemic heart disease.
authors.affiliation: Center for Perinatal Biology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, California, United States of America.
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, United States of America.|Department of Traditional Chinese Medicine, Shanghai Putuo District People's Hospital, Shanghai, PR China.
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, United States of America.
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, United States of America.
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, United States of America.
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, United States of America.
authors.forename: Lubo
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D003326:Coronary Circulation / Q000187:drug effects; D004198:Disease Susceptibility; D004353:Drug Evaluation, Preclinical; D005260:Female; D005333:Fetus / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D015918:Infusion Pumps, Implantable; D008297:Male; D008954:Models, Biological; D017202:Myocardial Ischemia / Q000209:etiology* / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000517:prevention & control; D009538:Nicotine / Q000008:administration & dosage / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D010641:Phenotype; D010766:Phosphorylation / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051744:Protein Kinase C-epsilon / Q000096:biosynthesis; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species; D020127:Recovery of Function; D018487:Ventricular Dysfunction, Left / Q000209:etiology* / Q000517:prevention & control
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D009538:Nicotine; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051744:Protein Kinase C-epsilon; D038362:Glycogen Synthase Kinase 3; D000111:Acetylcysteine