Abstract:

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 hyperpolarizing 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.

Key words: 7-[2-(4-Morpholinyl) ethoxy]chroman hydrochloride, Vasorelaxation, EDHF