Document Detail


Pravastatin attenuates hypertension, oxidative stress, and angiogenic imbalance in rat model of placental ischemia-induced hypertension.
MedLine Citation:
PMID:  23460290     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Preeclampsia is a pregnancy-specific condition characterized by an imbalance of circulating angiogenic factors and new-onset hypertension. Although current treatment options are limited, recent studies suggest that pravastatin may improve angiogenic profile and reduce blood pressure in preeclampsia. We hypothesized pravastatin would restore angiogenic balance and reduce mean arterial pressure (MAP) in rats with reduced utero-placental perfusion pressure (RUPP)-induced hypertension. Pravastatin was administered intraperitoneally (1 mg/kg per day) in RUPP (RUPP+P) and normal pregnant rats (NP+P) from day 14 to 19 of pregnancy. On day 19, MAP was measured via catheter, conceptus data were recorded, and tissues collected. MAP was increased (P<0.05) in RUPP compared with NP dams, and pravastatin ameliorated this difference. Pravastatin attenuated decreased fetal weight and plasma vascular endothelial growth factor and the RUPP-induced increased soluble fms-like tyrosine kinase-1 when compared with NP dams. Pravastatin treatment did not improve angiogenic potential in RUPP serum and decreased (P<0.05) endothelial tube formation in NP rats. RUPP rats presented with indices of oxidative stress, such as increased placental catalase activity and plasma thiobarbituric acid reactive substances along with decreased plasma total antioxidant capacity compared with NP controls, and pravastatin attenuated these effects. MAP, fetal weight, plasma vascular endothelial growth factor, and plasma soluble fms-like tyrosine kinase-1 were unchanged in NP+P compared with NP controls. The present data indicate that treatment with pravastatin attenuates oxidative stress and lowers MAP in placental ischemia-induced hypertension, but may have negative effects on circulating angiogenic potential during pregnancy. Further studies are needed to determine whether there are long-term deleterious effects on maternal or fetal health after pravastatin treatment during pregnancy-induced hypertension or preeclampsia.
Authors:
Ashley J Bauer; Christopher T Banek; Karen Needham; Haley Gillham; Susan Capoccia; Jean F Regal; Jeffrey S Gilbert
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-03-04
Journal Detail:
Title:  Hypertension     Volume:  61     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-18     Completed Date:  2013-07-05     Revised Date:  2014-10-22    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1103-10     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Blood Pressure / drug effects,  physiology
Cells, Cultured
Disease Models, Animal
Female
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology,  therapeutic use
Hypertension / etiology,  physiopathology,  prevention & control*
Ischemia / complications*
Neovascularization, Physiologic / drug effects*,  physiology
Oxidative Stress / drug effects*,  physiology
Placenta / blood supply*
Pravastatin / pharmacology*,  therapeutic use*
Pre-Eclampsia / prevention & control
Pregnancy
Rats
Rats, Sprague-Dawley
Thiobarbituric Acid Reactive Substances / metabolism
Trophoblasts / cytology,  drug effects,  metabolism
Vascular Endothelial Growth Factor A / blood
Vascular Endothelial Growth Factor Receptor-1 / blood
Grant Support
ID/Acronym/Agency:
HL114096/HL/NHLBI NIH HHS; NIH HL109843/HL/NHLBI NIH HHS; R01 HL114096/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 0/Thiobarbituric Acid Reactive Substances; 0/Vascular Endothelial Growth Factor A; EC 2.7.10.1/Flt1 protein, rat; EC 2.7.10.1/Vascular Endothelial Growth Factor Receptor-1; KXO2KT9N0G/Pravastatin
Comments/Corrections

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


Previous Document:  New Renin Inhibitor VTP-27999 Alters Renin Immunoreactivity and Does Not Unfold Prorenin.
Next Document:  Congenic mapping and sequence analysis of the Renin locus.