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), 1H-[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 CaCl₂-induced contracted rings and reduced the contraction induced by phenylephrine (10 μM) and caffeine (20 mM) in a Ca²⁺-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, Ca²⁺ influx through Ca²⁺ channels and intracellular Ca²⁺ 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.