title: Rutaecarpine inhibits angiotensin II-induced proliferation in rat vascular smooth muscle cells.
abstract: OBJECTIVE
  To evaluate the effects and possible mechanisms of rutaecarpine on angiotensin II (Ang II)-induced proliferation in cultured rat vascular smooth muscle cells (VSMCs).
  
  
  METHODS
  VSMCs were isolated from Male Sprague-Dawley rat aorta, and cultured by enzymic dispersion method. Experiments were performed with cells from passages 3-8. The cultured VSMCs were randomly divided into control, model (Ang II 0.1 μmol/L), and rutaecarpine (0.3-3.0 μmol/L) groups. VMSC proliferation was induced by Ang II, and was evaluated by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay and cell counting. To examine the mechanisms involved in anti-proliferative effects of rutaecarpine, nitric oxide (NO) levels and NO synthetase (NOS) activity were determined. Expressions of VSMC proliferation-related genes including endothelial nitric oxide synthase (eNOS), and c-myc hypertension related gene-1 (HRG-1) were determined by real-time reverse transcription-polymerase chain reaction (RT-PCR).
  
  
  RESULTS
  Rutaecarpine (0.3-3.0 μmol/L) inhibited Ang II-induced VSMC proliferation and the best effects were achieved at 3.0 μmol/L. The Ang II-induced decreases in cellular NO contents and NOS activities were antagonized by rutaecarpine (P <0.05). Ang II administration suppressed the expressions of eNOS and HRG-1, while increased c-myc expression (P <0.05). All these effects were attenuated by 3.0 μmol/L rutaecarpine (P <0.05).
  
  
  CONCLUSIONS
  Rutaecarpine is effective against Ang II-induced rat VSMC proliferation, and this effect is due, at least in part, to NO production and the modulation of VMSC proliferation-related gene expressions.
authors.affiliation: Key Laboratory of Basic Pharmacology of Guizhou and Department of Pharmacology, Zunyi Medical College, Zunyi, Guizhou Province, 563000, China.
authors.forename: Yan-ju
authors.initials: YJ
authors.lastname: Li
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Qi-hai
authors.initials: QH
authors.lastname: Gong
authors.forename: Qin
authors.initials: Q
authors.lastname: Wu
authors.forename: Li-mei
authors.initials: LM
authors.lastname: Yu
authors.forename: An-sheng
authors.initials: AS
authors.lastname: Sun
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D017931:DNA Primers; D006420:Hemeproteins / Q000378:metabolism; D026121:Indole Alkaloids / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D052999:Quinazolinones
chemical_list: D000804:Angiotensin II; D017931:DNA Primers; D006420:Hemeproteins; D026121:Indole Alkaloids; D052250:Nitric Oxide Synthase Type III; D016271:Proto-Oncogene Proteins c-myc; D011799:Quinazolines; C028632:rutecarpine; D052999:Quinazolinones