title: Agonistic autoantibodies to the angiotensin II type I receptor cause pathophysiologic characteristics of preeclampsia.
abstract: BACKGROUND
  Preeclampsia (PE), new-onset hypertension with proteinuria during pregnancy, is associated with increased reactive oxygen species, the vasoactive peptide endothelin-1 (ET-1), T and B lymphocytes, soluble antiangiogenic factors sFlt-1 and sEndoglin (sFlt-1 and sEng), and agonistic autoantibodies to the angiotensin II type I receptor (AT1-AA).
  
  
  OBJECTIVE
  One important area of investigation for our laboratory was to determine what role AT1-AA plays in the pathophysiology associated with PE.
  
  
  METHODS
  To achieve this goal, we examined the effect of AT1-AA suppression on hypertension in response to placental ischemia as well as the effect of AT1-AA on increased blood pressure, ET-1, reactive oxygen species, and sFlt-1 in normal pregnant rats (NP).
  
  
  RESULTS
  We demonstrated reductions in uterine perfusion pressure (RUPP) to be a stimulus for AT1-AA during pregnancy. We utilized the technique of B-cell depletion to suppress circulating AT1-AA in RUPP rats and found that AT1-AA suppression in RUPP rats was associated with lower blood pressure and ET-1 activation. To determine a role for AT1-AA to mediate hypertension during pregnancy, we infused purified rat AT1-AA (1:50) into NP rats, and analyzed blood pressure and soluble factors. We consistently found that AT1-AA infused rats had significantly increased AT1-AA and blood pressure above NP rats. This hypertension was associated with significantly increased ET-1 in renal cortices (11-fold) and placenta (4-fold), and there was an approximately 2- to 3-fold increase in placental oxidative stress. Furthermore, antiangiogenic factors sFlt-1 and sEng were significantly increased in the AT1-AA induced hypertensive group compared with the NP controls.
  
  
  CONCLUSIONS
  Collectively, these data indicated an important role for AT1-AA stimulated in response to placental ischemia that caused hypertension during pregnancy.
authors.affiliation: Departments of Obstetrics and Gynecology/Physiology, University of Mississippi Medical Center, Jackson, MS 39216-4505, USA. bblamarca@physiology.umsmed.edu
authors.forename: Babbette
authors.initials: B
authors.lastname: LaMarca
authors.forename: Marc R
authors.initials: MR
authors.lastname: Parrish
authors.forename: Kedra
authors.initials: K
authors.lastname: Wallace
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D005260:Female; D006801:Humans; D046110:Hypertension, Pregnancy-Induced / Q000276:immunology*; D007511:Ischemia / Q000276:immunology; D010920:Placenta / Q000098:blood supply; D011225:Pre-Eclampsia / Q000276:immunology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000276:immunology*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001323:Autoantibodies; D044140:Receptor, Angiotensin, Type 1