title: Antenatal nicotine induces heightened oxidative stress and vascular dysfunction in rat offspring.
abstract: OBJECTIVE
  Antenatal nicotine exposure causes aberrant vascular reactivity and increased blood pressure in adult male rat offspring in a sex-dependent manner. The present study tested the hypothesis that maternal nicotine administration increases the production of reactive oxygen species resulting in the vascular hypertensive reactivity in male offspring.
  
  
  METHODS
  Nicotine was administered to pregnant rats via subcutaneous osmotic minipumps throughout the gestation. The vascular oxidative damage and dysfunction were determined in 5-month-old male offspring. Contraction studies were performed on isolated aortas and their expression of NADPH oxidase (Nox2)/gp91 and nox4 determined by Western blot analysis. In addition, oxidative damage in the vessel wall was determined by measuring malondialdehyde concentrations, vascular superoxide production and SOD activity.
  
  
  RESULTS
  Antenatal nicotine significantly increased angiotensin II-induced arterial contractions in the offspring. The exaggerated vascular contractions were inhibited by both apocynin (a Nox inhibitor) and tempol (a SOD mimetic) in a concentration-dependent manner. In addition, ACh-induced relaxations were impaired in aortas isolated from the nicotine-treated offspring, which were restored by both apocynin and tempol in a concentration-dependent manner. The nicotine treatment significantly decreased the superoxide dismutase activity and increased malondialdehyde, superoxide and nitrotyrosine protein levels in the vascular wall. Consistently, antenatal nicotine exposure significantly enhanced the protein expression of NADPH oxidase Nox2/gp91, but not Nox4 in the aorta.
  
  
  CONCLUSIONS
  The present findings suggest that antenatal nicotine exposure results in the programming of heightened oxidative stress and vascular hypertensive reactivity via a Nox2-dependent mechanism, leading to an increased risk of hypertension in adult offspring.
authors.affiliation: Center for Perinatal Biology, Division of Pharmacology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA. dxiao@llu.edu
authors.forename: Daliao
authors.initials: D
authors.lastname: Xiao
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Huang
authors.forename: Shumei
authors.initials: S
authors.lastname: Yang
authors.forename: Lubo
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000254:growth & development / Q000503:physiopathology; D015153:Blotting, Western; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006973:Hypertension / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D009538:Nicotine / Q000009:adverse effects*; D018384:Oxidative Stress / Q000187:drug effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013113:Spin Labels; D013482:Superoxide Dismutase / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D000098:Acetophenones; D003497:Cyclic N-Oxides; D008562:Membrane Glycoproteins; D013113:Spin Labels; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D008315:Malondialdehyde; D009538:Nicotine; C056165:acetovanillone; D013482:Superoxide Dismutase; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498911:Nox4 protein, rat; C001803:tempol