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. STUDY DESIGN: 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. CONCLUSION: 17 OHP blunts hypertension associated with RUPP, possibly via suppression of cytokine-stimulated ET-1 activation.