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

• Published in: Chinese journal of integrative medicine Vol. 20; no. 9; pp. 682 - 687
• Main Author: 李艳菊 张锋 龚其海 吴芹 余丽梅 孙安盛
• Format: Journal Article
• Language: English
• Published: Heidelberg Chinese Association of Traditional and Western Medicine 01.09.2014
• Subjects: Angiotensin II - pharmacology; Animals; Base Sequence; Cell Proliferation - drug effects; Cells, Cultured; DNA Primers; Hemeproteins - metabolism; Indole Alkaloids - pharmacology; Male; Medicine; Medicine & Public Health; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - drug effects; Nitric Oxide Synthase Type III - metabolism; Original Article; Proto-Oncogene Proteins c-myc - metabolism; Quinazolines - pharmacology; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; Sprague-Dawley; 内皮型一氧化氮合酶; 吴茱萸次碱; 大鼠; 抗增殖作用; 血管平滑肌细胞; 血管紧张素; 诱导; rutaecarpine; nitric oxide; vascular smooth muscle cell proliferation; angiotensin II; gene expression
• ISSN: 1672-0415; 1993-0402; 1993-0402
• DOI: 10.1007/s11655-013-1198-4

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.