title: 17-Hydroxyprogesterone blunts the hypertensive response associated with reductions in uterine perfusion pressure in pregnant rats.
abstract: OBJECTIVE
  Reduction in uteroplacental perfusion (RUPP) in pregnant rats is associated with hypertension, elevated cytokines, and activation of the endothelin (ET-1) system. Our objective was to determine whether the antiinflammatory properties of 17-alpha-hydroxyprogesterone caproate (17 OHP) reduce cytokine-stimulated vasoactive pathways that are associated with hypertension in response to placental ischemia.
  
  
  METHODS
  Mean arterial pressure (MAP), tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, and renal ET-1 were measured in the following: pregnant controls, pregnant controls plus 17 OHP (6.6 mg/kg), RUPP rats, and RUPP rats plus 17 OHP.
  
  
  RESULTS
  MAP increased 29 mm Hg in RUPP rats compared with pregnant controls (P < .001), whereas in RUPP plus 17 OHP rats, MAP increased only 19 mm Hg (P < .05). TNF-alpha and IL-6 increased 2- to 3-fold, respectively, in response to placental ischemia but was normalized in RUPP rats treated with 17 OHP. ET-1 increased 3-fold in RUPP rats but was markedly less in RUPP plus 17 OHP rats.
  
  
  CONCLUSIONS
  17 OHP blunts hypertension associated with RUPP, possibly via suppression of cytokine-stimulated ET-1 activation.
authors.affiliation: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Mississippi Medical Center, Jackson, MS 39216-4505, USA.
authors.forename: Edward W
authors.initials: EW
authors.lastname: Veillon
authors.forename: Sharon D
authors.initials: SD
authors.lastname: Keiser
authors.forename: Marc R
authors.initials: MR
authors.lastname: Parrish
authors.forename: William
authors.initials: W
authors.lastname: Bennett
authors.forename: Kathy
authors.initials: K
authors.lastname: Cockrell
authors.forename: Lillian F
authors.initials: LF
authors.lastname: Ray
authors.forename: Joey P
authors.initials: JP
authors.lastname: Granger
authors.forename: James N
authors.initials: JN
authors.lastname: Martin
authors.forename: Babbette
authors.initials: B
authors.lastname: LaMarca
mesh_terms: D000077713:17 alpha-Hydroxyprogesterone Caproate; D019326:17-alpha-Hydroxyprogesterone / Q000494:pharmacology*; D000818:Animals; D019332:Endothelin-1 / Q000502:physiology; D005260:Female; D006908:Hydroxyprogesterones / Q000494:pharmacology; D007511:Ischemia / Q000188:drug therapy / Q000503:physiopathology; D010920:Placenta / Q000098:blood supply; D021041:Placental Circulation / Q000187:drug effects* / Q000502:physiology*; D011247:Pregnancy; D045167:Progesterone Congeners / Q000494:pharmacology; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D019332:Endothelin-1; D006908:Hydroxyprogesterones; D045167:Progesterone Congeners; D014409:Tumor Necrosis Factor-alpha; D000077713:17 alpha-Hydroxyprogesterone Caproate; D019326:17-alpha-Hydroxyprogesterone