Oxidative stress contributes to soluble fms-like tyrosine kinase-1 induced vascular dysfunction in pregnant rats
| Autor: | Michael J. Ryan, Drew Colson, Sara A.B. Gilbert, Jason P. Bridges, Jeffrey S. Gilbert, Matthew P. Dukes, Joey P. Granger |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Nitroprusside
medicine.medical_specialty Endothelium Vasodilation Blood Pressure medicine.disease_cause Article Preeclampsia Pregnancy Superoxides Internal medicine Internal Medicine medicine Animals Endothelial dysfunction Fetal Growth Retardation Vascular Endothelial Growth Factor Receptor-1 business.industry medicine.disease Rats Vascular endothelial growth factor A Oxidative Stress medicine.anatomical_structure Endocrinology embryonic structures Pregnancy Animal Female Sodium nitroprusside business Soluble fms-like tyrosine kinase-1 Oxidative stress medicine.drug |
| Zdroj: | American journal of hypertension. 22(5) |
| ISSN: | 1941-7225 |
| Popis: | BACKGROUND—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 the soluble VEGF receptor (sFlt-1) contribute to endothelial dysfunction in preeclampsia. We hypothesized that chronic infusion of sFlt-1 to mimic the increase observed in preeclamptic patients would reduce plasma VEGF concentrations, increase blood pressure (BP) and vascular superoxide levels, and cause endothelial dysfunction in the pregnant rat. METHODS—Recombinant sFlt-1 was infused (500 ng/h) during days 13–18 of pregnancy. BP, fetal and placental weight, oxidative stress and vessel vasorelaxation were determined on day 18 of pregnancy. RESULTS—Plasma sFlt-1 concentrations (299 ± 33 vs. 100 ± 16 pg/ml; P < 0.01) and BP (117 ± 6 vs. 98 ± 4 mm Hg; P < 0.01) were increased, while plasma-free VEGF concentrations (570 ± 77 vs. 780 ± 48 pg/ml; P < 0.01) were decreased when compared to vehicle infused dams. sFlt-1 rats had smaller fetuses (1.3 ± 0.03 vs. 1.5 ± 0.04 g, P < 0.01) and placentas (0.41 ± 0.01 vs. 0.47 ± 0.02 g; P < 0.05). Placental (180 ± 66 vs. 24 ± 2.3 RLU/min/mg; P < 0.05) and vascular (34 ± 8 vs. 12 ± 5 RLU/min/mg; P < 0.05) superoxide production was increased in the sFlt-1 compared to vehicle infused rats. Vasorelaxation to acetylcholine (Ach) and sodium nitroprusside (SNP) were both decreased (P < 0.05) in the sFlt-1 infusion group compared to the vehicle and this decrease was attenuated (P < 0.05) by the superoxide scavenger Tiron. CONCLUSION—These data indicate elevated maternal sFlt-1 and decreased VEGF concentrations results in increased oxidative stress that contributes to vascular dysfunction during pregnancy. |
| Databáze: | OpenAIRE |
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