This study aimed to investigate the relaxant effect of chroman compound HEF-04 on isolated vascular smooth muscle （VSM） and the possible underlying mechanisms involved. Isolated rabbit thoracic aorta was used as the in vitro model and the relaxant effects of HEF-04 on endothelium-intact （＋EC） and endothelium-denuded （EC） thoracic aortic rings were compared. Potassium channel blockers, guanylate cyclase inhibitors, and COX-inhibitors were used to explore associations between the relaxant effects of HEF-04 with potassium channels, NO, and prostaglandin-like substances and endothelial hyperpolafizing factor （EDHF）, respectively. The results indicated that HEF-04 （1 × 10^-5 mol/L to 3× 10^-3 mol/L） had no significant impact on basal vascular tension, but could relax the contraction of vascular smooth muscle caused by high-K＋ solution in a dose-dependent manner. Indomethacin （5.6× 10^-6 mol/L） had no effect on vasorelaxation effect of HEF-04. In contrast, the vasorelaxant effect of HEF-04 was enhanced by methylene blue, which was significantly inhibited by calcium-dependent potassium channel blocker TEA. The vasorelaxant effect of HEF-04 on ＋EC thoracic aortic rings was significantly stronger than that on -EC thoracic aortic rings. The endothelium dependent relaxant effect of HEF-04 on VSM might be attributed to the interaction of HEF-04 with vascular relaxing factors or the increased release of EDHF.
The purpose of this study was to examine the relaxation effect of CY on the vascular smooth muscle （VSM） from rabbits. Experiments were carried out on isolated thoracic aorta of rabbits. CY （3 x 103 mM- 3 mM） could relax the VSM preparations pre-contracted by adrenaline （AD）, noradrenaline （NE）, high-K^＋ solution or BaCl2 with respective EC50 values of （0.3 1±0.11） mM, 0.19±0.03 mM, 0.20±0.04 mM and 0.25±0.04 mM. Moreover, CY （10-2 mM, 0.1 mM and 1 mM） inhibited norepinephrine （NE）, CaCl2 and KCl-induced vasoconstriction in a concentration dependent manner. The phasic contraction produced by NE was concentration dependently attenuated with CY （10^-2 mM, 0.1 mM and 1 mM） in calcium-free medium, similar to that caused by verapamil. The present findings suggest that CY relaxed thoracic aortic rings by blocking voltage-dependent Ca^2＋ channels. The inhibition of intracellular Ca^2＋ release may be one of the main vasorelaxant mechanisms of CY.
