Rutaecarpine Inhibits Angiotensin Ⅱ-Induced Proliferation in Rat Vascular Smooth Muscle Cells

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 μ moVL）, and rutaecarpine （0.3-3.0μmol/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 chain reaction （RT-PCR）. Results： Rutaecarpine （0.3-3.0μmol/l_） inhibited Ang R-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 3.0μmol/L rutaecarpine （P〈0.05）. Conclusion： 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.

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 μ moVL）, and rutaecarpine （0.3-3.0μmol/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 chain reaction （RT-PCR）. Results： Rutaecarpine （0.3-3.0μmol/l_） inhibited Ang R-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 3.0μmol/L rutaecarpine （P〈0.05）. Conclusion： 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.