Open AccessRegulation of soluble fms‐like tyrosine kinase‐1 production in response to placental ischemia/hypoxia: role of angiotensin II
Author(s) -
Murphy Sydney R.,
Cockrell Kathy
Publication year - 2015
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.12310
Subject(s) - hypoxia (environmental) , angiotensin ii , soluble fms like tyrosine kinase 1 , tyrosine kinase , ischemia , medicine , tyrosine , renin–angiotensin system , microbiology and biotechnology , chemistry , endocrinology , placental growth factor , biology , biochemistry , signal transduction , oxygen , receptor , vegf receptors , vascular endothelial growth factor , organic chemistry , blood pressure
While soluble fms‐like tyrosine‐1 (sFlt‐1) is implicated in the pathogenesis of hypertension during preeclampsia, the mechanisms leading to the enhanced sFlt‐1 production remain unclear. A recent report suggests exogenous angiotensin II ( ANGII ) stimulates sFlt‐1 production in pregnant rats, however, the role of endogenous ANGII in mediating the placental production of sFlt‐1 in response to placental ischemia remains unknown. Therefore, the purpose of this study was to determine the role of endogenous ANGII in mediating the placental production of sFlt‐1 in response to placental ischemia in pregnant Sprague–Dawley rats. To this end we compared sFlt‐1 and ANGII levels from placental explants collected from normal pregnant ( NP ) and Reduced Uterine Perfusion Pressure ( RUPP ) rats. sF lt‐1 (3271 ± 264 vs. 2228 ± 324 pg/mL, P < 0.05) and ANGII levels (43.2 ± 2.8 vs. 26.7 ± 1.9 pg/mL, P < 0.05) were higher in placental explants from RUPP rats versus NP rats. Administration of Losartan, an angiotensin type 1 ( AT 1 ) receptor antagonist, (10 mg/day for 5 days) to RUPP rats significantly reduced plasma levels of sF lt‐1 (1432 ± 255 pg/mL, P < 0.05) when compared with untreated control rats (3431 ± 454 pg/mL). In addition, RUPP ‐induced hypertension was significantly reduced (113 ± 2 mmHg vs. 139 ± 2 mmHg, P < 0.05). In conclusion, placental sF lt‐1 and ANGII production are significantly elevated in response to placental ischemia in pregnant rats. In addition, AT 1 receptor activation, by endogenous ANGII , appears to play an important role in mediating the placental production of sF lt‐1 in response to placental ischemia in pregnant rats.