Endothelium-dependent and endothelium-independent vasorelaxant effects of tiliacorinine 12′-O-acetate and mechanisms on isolated rat aorta

Tiliacorinine 12′- O -acetate is a modified analog of Tiliacorinine, a major compound in Tiliacora triandra. The present study explored the vasorelaxation property of tiliacorinine 12′- O -acetate and its mechanism in isolated rat aorta using the organ bath technique. Tiliacorinine 12′- O -acetate exhibited concentration-dependent (10 −15 –10 −3.5 M) vasorelaxation in endothelium-intact rings (E max = 93.53 ± 2.79%) and endothelium-denuded rings (E max = 74.31 ± 5.09%). The effects of tiliacorinine 12′- O -acetate were attenuated by pre-incubation with N(ω)-nitro- l -arginine methyl ester (L-NAME, endothelium nitric oxide synthase inhibitor) (100 μM), 1 H -[1,2,4]oxadiazolo[4,3- a ]quinoxalin-1-one (ODQ, soluble quanylylcyclase inhibitor) (1 μM), and 4-aminopyridine (1 mM, K v channel blocker). However, this effect was not impacted by indomethacin (10 μM, cyclooxygenase inhibitor), tetraethylammonium (5 mM, K ca channel blocker), barium chloride (1 mM, K IR channel blocker), or glibenclamide (10 μM, K ATP channel blocker). Moreover, pretreatment with tiliacorinine 12′- O -acetate reduced the effect of L-NAME (100 μM) on acetylcholine-induced vasorelaxation. Tiliacorinine 12′- O -acetate showed inhibitory effects on CaCl 2 -induced contracted rings and reduced the contraction induced by phenylephrine (10 μM) and caffeine (20 mM) in a Ca 2+ -free solution. The results of this study suggest that tiliacorinine 12′- O -acetate induced endothelium-dependent vasorelaxation through the eNOS/NO/sGC pathway, and also induced endothelium independent vasorelaxation involving the modulation of sGC activity, K v channels, Ca 2+ influx through Ca 2+ channels and intracellular Ca 2+ release. The data concerning the benefits of tiliacorinine 12′- O -acetate might be further investigated for the application of tiliacorinine 12′- O -acetate as an antihypertensive compound.