Document Detail


Oxidative stress contributes to soluble fms-like tyrosine kinase-1 induced vascular dysfunction in pregnant rats.
MedLine Citation:
PMID:  19265787     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 acetylecholine (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.
Authors:
Jason P Bridges; Jeffrey S Gilbert; Drew Colson; Sara A Gilbert; Matthew P Dukes; Michael J Ryan; Joey P Granger
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2009-03-05
Journal Detail:
Title:  American journal of hypertension     Volume:  22     ISSN:  1941-7225     ISO Abbreviation:  Am. J. Hypertens.     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-04-23     Completed Date:  2009-05-28     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  8803676     Medline TA:  Am J Hypertens     Country:  United States    
Other Details:
Languages:  eng     Pagination:  564-8     Citation Subset:  IM    
Affiliation:
Department of Physiology and the Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, Mississippi, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Pressure / drug effects
Female
Fetal Growth Retardation / etiology
Nitroprusside / pharmacology
Oxidative Stress / physiology*
Pregnancy
Pregnancy, Animal / blood,  physiology
Rats
Superoxides / metabolism
Vascular Endothelial Growth Factor Receptor-1 / physiology*
Vasodilation / drug effects
Grant Support
ID/Acronym/Agency:
HL51971/HL/NHLBI NIH HHS; HL85907/HL/NHLBI NIH HHS; HL90269/HL/NHLBI NIH HHS; P01 HL051971-165259/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
11062-77-4/Superoxides; 15078-28-1/Nitroprusside; EC 2.7.10.1/Flt1 protein, rat; EC 2.7.10.1/Vascular Endothelial Growth Factor Receptor-1
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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