| Abstract: | Proliferation of vascular smooth muscle cells (VSMCs) is a crucial event in cardiovascular diseases. Isorhynchophylline, an alkaloid from a traditional Chinese medicine Gambirplant, has been used to treat cardiovascular diseases. The aim of this study was to investigate the effects of isorhynchophylline on angiotensin II (Ang II)‐induced proliferation of rat VSMCs. VSMCs were isolated from rat artery and cultured for 14 days before experimentation. The effect of isorhynchophylline on Ang II‐induced proliferation was evaluated by cell number, MTT assay and flow cytometry, and nitric oxide (NO) content and activity of NO synthase (NOS) were measured. The expression of proto‐oncogene c‐fos, osteopontin (OPN) and proliferating cell nuclear antigen (PCNA) mRNAs was measured by real‐time RT‐PCR. VSMC cultures were verified by morphology and immunostaining with α‐smooth muscle actin. Isorhynchophylline (0.1–10.0 μM) was not toxic to VSMCs, but markedly decreased Ang II (1.0 μm )‐enhanced cell number and MTT intensity, and blocked cell transition from G0/G1 to S phase. Furthermore, isorhynchophylline increased the NO content and NOS activity, and suppressed Ang II‐induced over‐expression of c‐fos, OPN and PCNA. Thus, isorhynchophylline was effective against Ang‐II induced cell proliferation, an effect that appears to be due, at least in part, to increased NO production, regulation of the cell cycle, and depressed expression of c‐fos, OPN and PCNA related to VMSC proliferation. |
