title: Expression of endothelial angiotensin II receptor mRNA in pregnancy-induced hypertension.
abstract: OBJECTIVE
  The normal suppression of vascular sensitivity to angiotensin II (Ang II) in pregnancy is lost in pregnancy-induced hypertension (PIH). To examine the mechanism, we investigated Ang II receptor subtype 1 (AT1R) and 2 (AT2R) expression in human umbilical vein endothelial cells (HUVEC) and vascular smooth muscle cells (VSMC).
  
  
  METHODS
  The HUVEC and VSMC were incubated with serum from normal pregnant women and PIH patients for 0 to 12 h. The AT1R and AT2R mRNA were semiquantified as the ratio to glyceraldehyde-3-phosphate dehydrogenase mRNA, using multiplex reverse transcription-polymerase chain reaction. The AT1R expression was also evaluated by immunocytochemistry.
  
  
  RESULTS
  Serum from PIH patients significantly increased AT1R mRNA of HUVEC (1.48 +/- 0.44) after a 12-h incubation compared with that from normal pregnant women (0.25 +/- 0.14). On the other hand, AT2R mRNA of HUVEC incubated with serum from PIH patients (0.14 +/- 0.02) was significantly decreased compared with HUVEC incubated with serum from normal pregnant women (0.31 +/- 0.08). The AT1R mRNA of VSMC was significantly increased by serum from both PIH patients and normal pregnant women. The AT1R-to-AT2R mRNA ratio increased by serum from PIH patients was significantly reduced by anti-tumor necrosis factor-alpha (TNF-alpha) antibody (20 microg/mL). Valsartan (an AT1R antagonist, at 1 to 10 nmol/L) significantly increased AT2R mRNA of HUVEC. Also, immunocytochemistry demonstrated that endothelial AT1R expression was strongly increased by PIH sera and reduced by anti-TNF-alpha antibody.
  
  
  CONCLUSIONS
  Endothelial AT1R expression is increased and AT2R expression is decreased in PIH. The TNF-alpha is related to the pathogenesis of PIH by reduced AT2R mRNA through an increase of AT1R mRNA.
authors.affiliation: Department of Obstetrics and Gynecology, Ehime University School of Medicine, Ehime, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Takeda-Matsubara
authors.forename: Keiichi
authors.initials: K
authors.lastname: Matsubara
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ochi
authors.forename: Masaharu
authors.initials: M
authors.lastname: Ito
authors.forename: Masaru
authors.initials: M
authors.lastname: Iwai
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Horiuchi
mesh_terms: D000328:Adult; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis*; D011945:Receptors, Angiotensin / Q000096:biosynthesis*; D014471:Umbilical Veins / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D011945:Receptors, Angiotensin