title: Effect of sodium tanshinone IIA sulfonate treatment in a rat model of preeclampsia.
abstract: Preeclampsia is a disorder of pregnancy with a significant impact on maternal and fetal health. The complexity of this multifactorial condition has precluded development of effective therapies and, although many potential pathways have been investigated, the etiology still requires clarification. Our group has investigated the scavenger lectin-like oxidized LDL (LOX-1) receptor, which may respond to factors released from the distressed placenta that contribute to the vascular pathologies observed in preeclampsia. Given the known beneficial effects of sodium tanshinone IIA sulfonate (STS; a component of Salvia miltiorrhiza) on vasodilation, reduction of oxidative stress, and lipid profiles, we have investigated its role as a potential treatment strategy. We hypothesized that STS would improve vascular endothelial function and, combined with a reduction in oxidative stress, would improve pregnancy outcomes in a rat model of preeclampsia (reduced uteroplacental perfusion pressure, RUPP). We further hypothesized this may occur via the action of STS on the LOX-1 and/or platelet-activating factor (PAF) receptor axes. The RUPP model increased maternal blood pressure, vascular oxidative stress, and involvement of the vascular PAF receptor. Treatment with STS during pregnancy decreased both oxidative stress and involvement of the PAF receptor; however, it also increased involvement of the LOX-1 receptor, which is in line with the concept that scavenger receptors, such as LOX-1 and PAF, are upregulated in response to ligand binding and/or under pathological conditions. In this model of preeclampsia, however, the vascular actions of STS did not lead to improvements in pregnancy outcome such as fetal biometrics or maternal blood pressure.
authors.affiliation: Department of Obstetrics and Gynaecology, University of Alberta, Edmonton, Canada; Women and Children's Health Research Institute and the Cardiovascular Research Centre, Edmonton, Canada;
authors.forename: Jude S
authors.initials: JS
authors.lastname: Morton
authors.affiliation: Department of Obstetrics and Gynaecology, University of Alberta, Edmonton, Canada; Women and Children's Health Research Institute and the Cardiovascular Research Centre, Edmonton, Canada;
authors.forename: Anita
authors.initials: A
authors.lastname: Quon
authors.affiliation: Women and Children's Health Research Institute and the Cardiovascular Research Centre, Edmonton, Canada; Department of Pediatrics, University of Alberta, Edmonton, Canada;
authors.forename: Po-Yin
authors.initials: PY
authors.lastname: Cheung
authors.affiliation: Department of Vascular Physiology, National Cerebral and Cardiovascular Centre Research Institute, Suita, Osaka, Japan; and.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Sawamura
authors.affiliation: Department of Obstetrics and Gynaecology, University of Alberta, Edmonton, Canada; Women and Children's Health Research Institute and the Cardiovascular Research Centre, Edmonton, Canada; Department of Physiology, University of Alberta, Edmonton, Canada sandra.davidge@ualberta.ca.
authors.forename: Sandra T
authors.initials: ST
authors.lastname: Davidge
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D008077:Lipoproteins, LDL / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D010616:Phenanthrenes / Q000494:pharmacology*; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism; D011225:Pre-Eclampsia / Q000188:drug therapy*; D011247:Pregnancy; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects
chemical_list: D008077:Lipoproteins, LDL; D010616:Phenanthrenes; C099252:oxidized low density lipoprotein; C024894:tanshinone II A sodium sulfonate
keywords: LOX-1; PAF receptor; preeclampsia; pregnancy; tanshinone; vascular function