title: Role of nitric oxide and reactive oxygen species in the pathogenesis of preeclampsia.
abstract: OBJECTIVE
  Preeclampsia is characterized by a disruption of general vascular dilatation, which is mainly mediated by nitric oxide (NO) and disturbed by reactive oxygen species (ROS). The present study investigated the roles of NO and ROS in the pathogenesis of preeclampsia.
  
  
  METHODS
  Serum samples were obtained prospectively. Serum levels of NO(2)/NO(3) (NOx) and creatol (CTL), the oxidized metabolite of creatine, and flow-mediated dilatation (FMD) of brachial artery were measured in normal pregnant women and preeclamptic patients. To evaluate the effect of circulating factors that control vascular function NO synthase (NOS) and NAD(P)H oxidase mRNA expression was evaluated in cultured human umbilical vein endothelial cells using reverse transcriptase polymerase chain reaction.
  
  
  RESULTS
  Serum NOx concentration was decreased and CTL concentration was increased in preeclamptic patients relative to healthy controls during the first trimester of pregnancy. Further, preeclamptic patients exhibited disrupted FMD, which was regulated in part by NO. Immunohistochemistry demonstrated strong expression of nitrotyrosine in the vasculature of preeclamptic placentas. Treatment with sera derived from preeclamptic patients increased endothelial expression of inducible NOS (iNOS) mRNA, and this increase was inhibited by angiotensin II (Ang II) receptor type 2 (AT2) blocker. Endothelial NAD(P)H oxidase subunit gp91(phox) expression was increased by treatment with sera from preeclamptic patients and this increase was attenuated by Ang II receptor type 1 (AT1) blocker.
  
  
  CONCLUSIONS
  The present findings suggest that NO and ROS play important roles in the pathogenesis of preeclampsia and that these roles involve Ang II.
authors.affiliation: Department of Obstetrics and Gynecology, Ehime University School of Medicine, Shitsukawa, Toon, Ehime 791-0295, Japan. keiichi@m.ehime-u.ac.jp
authors.forename: Keiichi
authors.initials: K
authors.lastname: Matsubara
authors.forename: Yuko
authors.initials: Y
authors.lastname: Matsubara
authors.forename: Shinji
authors.initials: S
authors.lastname: Hyodo
authors.forename: Tomihiro
authors.initials: T
authors.lastname: Katayama
authors.forename: Masaharu
authors.initials: M
authors.lastname: Ito
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D000804:Angiotensin II / Q000378:metabolism; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019255:NADPH Oxidases / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000209:etiology* / Q000378:metabolism; D011247:Pregnancy; D011261:Pregnancy Trimester, First / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D014471:Umbilical Veins / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D009569:Nitric Oxide; D019255:NADPH Oxidases