Abstract

Xinhua Zhang, Yongmei Han, Biqi Zhang and Shenjiang Hu*

To investigate the vasomotor effects of Cyclovirobuxine D (CVB) on the rat aortic rings in vitro and underlying mechanisms, rat aorta was obtained, and aortic rings with or without endothelium were pre-treated with potassium chloride (KCl) or phenylephrine (PE). Then, CVB was added and its vasomotor effects were observed. In addition, the influence of other drugs on the CVB induced vasomotor effects was detected. The effects of CVB and verapamil (VER) on the dilation of the aortic rings were observed. After incubation in Ca2+ free solution containing CVB, the KCl pre-treated aortic rings were treated with CaCl2 aiming to investigate the effects of CVB on the influx of extracellular calcium, or with PE and caffeine to observe the effects of CVB on the release of intracellular calcium. In aortic rings precontracted with PE or KCl, CVB produced concentration-dependent relaxation in both endothelium-intact and denuded rings. But the dilation of rings with intact endothelium was more potent than that of rings without endothelium. In intact rings, L-NAME (100 µmol/L) or indomethacin (10 µmol/L) reduced the degree of CVB-induced relaxation. CVB (3.2×10-4 mol/L) and VER (1 µmol/L) could induce the dilation of KCl precontracted rings and these effects could be partially reversed by CaCl2 (1.25 mmol/L). In Ca2+ free solution, calcium-dependent KCl contractions were inhibited by CVB (3.2×10-4 mol/L). Furthermore, CVB (3.2×10-4 mol/L) inhibited the PE (1 µmol/L) induced contraction of aortic rings, but had no effect on the caffeine (10 mmol/L) induced contraction. CVB vasodilates by endothelium-dependent and endothelium-independent mechanism, Endothelium-dependent involving nitric oxide or prostaglandin released from the endothelium. Its endothelium-independent vasodilation probably occurs via the suppression of voltage- sensitive Ca2+ channel and inhibition of IP3-sensitive Ca2+ released in vascular smooth muscles, but has no effect on ryanodine receptor.