title: Pravastatin attenuates hypertension, oxidative stress, and angiogenic imbalance in rat model of placental ischemia-induced hypertension.
abstract: 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: Department of Biomedical Sciences, University of Minnesota Medical School, Duluth, MN, USA.
authors: Ashley J
authors: AJ
authors: Bauer
authors: Christopher T
authors: CT
authors: Banek
authors: Karen
authors: K
authors: Needham
authors: Haley
authors: H
authors: Gillham
authors: Susan
authors: S
authors: Capoccia
authors: Jean F
authors: JF
authors: Regal
authors: Jeffrey S
authors: JS
authors: Gilbert
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D007511:Ischemia / Q000150:complications*; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010920:Placenta / Q000098:blood supply*; D017035:Pravastatin / Q000494:pharmacology* / Q000627:therapeutic use*; D011225:Pre-Eclampsia / Q000517:prevention & control; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017392:Thiobarbituric Acid Reactive Substances; D042461:Vascular Endothelial Growth Factor A; C501164:Flt1 protein, rat; D040281:Vascular Endothelial Growth Factor Receptor-1; D017035:Pravastatin