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Oxidative Stress mediates soluble Flt‐1 induced vascular dysfunction in pregnant rats
Author(s) -
Colson Drew,
Gilbert Jeffrey S,
Bridges Jason,
Dukes Matthew P,
Babcock Sara A,
Ryan Michael J,
Granger Joey P
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.969.7
Subject(s) - oxidative stress , endocrinology , preeclampsia , medicine , endothelial dysfunction , superoxide dismutase , sodium nitroprusside , vascular endothelial growth factor , soluble fms like tyrosine kinase 1 , chemistry , nitric oxide , placental growth factor , biology , pregnancy , vegf receptors , genetics
Recent evidence indicates that both increased oxidative stress and an altered balance between pro‐ and anti‐angiogenic factors such as vascular endothelial growth factor (VEGF) and soluble VEGF receptor Flt‐1 (sFlt‐1) contribute to hypertension in preeclampsia. Thus, we hypothesized that infusion of sFlt‐1 to levels that mimic preeclampsia would increase blood pressure, and vascular and placental oxidative stress, and cause vascular endothelial dysfunction in the pregnant rat. sFlt‐1 infusion elevated plasma sFlt‐1 concentration (299±33 vs. 100±16 pg/ml; P <0.01) three fold and increased blood pressure (117±6 vs. 98±4 mm Hg; P <0.01) when compared to saline infused rats. sFlt‐1 infusion also increased superoxide in the placenta (222 ± 71 vs. 40 ± 9 RLU/min/mg; P < 0.05) and the vasculature (34 ± 8 vs. 12 ± 5; P < 0.05) compared to the vehicle infused controls. Wire myography revealed that percent relaxation of vascular rings to acetylcholine and sodium nitroprusside were both decreased ( P <0.05) in the sFlt‐1 infusion group compared to the vehicle infusion group and this effect was attenuated by the superoxide dismutase mimetic Tiron (P<0.05). These data indicate that hypertension associated with elevated maternal concentrations of sFlt‐1 during pregnancy may be mediated, in part, by impaired vascular function as a result of increased oxidative stress.