Rutaecarpine inhibits angiotensin II-induced proliferation in rat vascular smooth muscle cells

To evaluate the effects and possible mechanisms of rutaecarpine on angiotensin II (Ang II)-induced proliferation in cultured rat vascular smooth muscle cells (VSMCs). 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 mu mol/L), and rutaecarpine (0.3-3.0 mu mol/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). Rutaecarpine (0.3-3.0 mu mol/L) inhibited Ang II-induced VSMC proliferation and the best effects were achieved at 3.0 mu mol/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 mu mol/L rutaecarpine (P < 0.05). 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.