title: The vascular effects of sodium tanshinone IIA sulphonate in rodent and human pregnancy.
abstract: Danshen, in particular its derivative tanshinone IIA (TS), is a promising compound in the treatment of cardiovascular diseases and has been used for many years in traditional Chinese medicine. Although many actions of TS have been researched, its vasodilator effects in pregnancy remain unknown. There have been a few studies that have shown the ability of TS to reduce blood pressure in women with hypertensive pregnancies; however, there are no studies which have examined the vascular effects of TS in the pregnant state in either normal or complicated pregnancies. Our aim was to determine the vasoactive role of TS in multiple arteries during pregnancy including: rat resistance (mesenteric and uterine) and conduit (carotid) arteries. Further, we aimed to assess the ability of TS to improve uterine blood flow in a rodent model of intrauterine growth restriction. Wire myography was used to assess vascular responses to the water-soluble derivative, sodium tanshinone IIA sulphonate (STS) or to the endothelium-dependent vasodilator, methylcholine. At mid-pregnancy, STS caused direct vasodilation of rat resistance (pEC50 mesenteric: 4.47±0.05 and uterine: 3.65±0.10) but not conduit (carotid) arteries. In late pregnancy, human myometrial arteries responded with a similar sensitivity to STS (pEC50 myometrial: 3.26±0.13). STS treatment for the last third of pregnancy in eNOS-/- mice increased uterine artery responses to methylcholine (Emax eNOS-/-: 55.2±9.2% vs. eNOS-/- treated: 75.7±8.9%, p<0.0001). The promising vascular effects, however, did not lead to improved uterine or umbilical blood flow in vivo, nor to improved fetal biometrics; body weight and crown-rump length. Further, STS treatment increased the uterine artery resistance index and decreased offspring body weight in control mice. Further research would be required to determine the safety and efficacy of use of STS in pregnancy.
authors: Department of Obstetrics and Gynaecology, University of Alberta, Edmonton, AB, Canada; Women and Children's Health Research Institute and the Cardiovascular Research Centre, Edmonton, AB, Canada.
authors: Jude S
authors: JS
authors: Morton
authors: Women and Children's Health Research Institute and the Cardiovascular Research Centre, Edmonton, AB, Canada; Department of Medicine, University of Alberta, Edmonton, AB, Canada.
authors: Irene J
authors: IJ
authors: Andersson
authors: Women and Children's Health Research Institute and the Cardiovascular Research Centre, Edmonton, AB, Canada; Department of Pediatrics, University of Alberta, Edmonton, AB, Canada.
authors: Po-Yin
authors: PY
authors: Cheung
authors: Gravida, National Research Centre for Growth and Development, Liggins Institute, University of Auckland, Auckland, New Zealand.
authors: Philip
authors: P
authors: Baker
authors: Department of Obstetrics and Gynaecology, University of Alberta, Edmonton, AB, Canada; Women and Children's Health Research Institute and the Cardiovascular Research Centre, Edmonton, AB, Canada; Department of Physiology, University of Alberta, Edmonton, AB, Canada.
authors: Sandra T
authors: ST
authors: Davidge
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects / Q000502:physiology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008810:Mice, Inbred C57BL; D010616:Phenanthrenes / Q000494:pharmacology*; D011247:Pregnancy; D011256:Pregnancy Outcome; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D014469:Umbilical Arteries / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D010616:Phenanthrenes; D014665:Vasodilator Agents; C024894:tanshinone II A sodium sulfonate