17-Hydroxyprogesterone blunts the hypertensive response associated with reductions in uterine perfusion pressure in pregnant rats.
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.
Veillon
Edward W
EW
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Mississippi Medical Center, Jackson, MS 39216-4505, USA.
Keiser
Sharon D
SD
Parrish
Marc R
MR
Bennett
William
W
Cockrell
Kathy
K
Ray
Lillian F
LF
Granger
Joey P
JP
Martin
James N
JN
LaMarca
Babbette
B
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
D019332:Endothelin-1; D006908:Hydroxyprogesterones; D045167:Progesterone Congeners; D014409:Tumor Necrosis Factor-alpha; D000077713:17 alpha-Hydroxyprogesterone Caproate; D019326:17-alpha-Hydroxyprogesterone