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(omega)-nitro-L-arginine methyl ester (L-NAME, endothelium nitric oxide synthase inhibitor) (100 mu M), 1H-[1,2,4] oxadiazolo[4,3-a] quinoxalin-1-one (ODQ, soluble quanylylcyclase inhibitor) (1 mu M), and 4aminopyridine (1 mM, K-v channel blocker). However, this effect was not impacted by indomethacin (10 mu M, cyclooxygenase inhibitor), tetraethylammonium (5 mM, K-ca channel blocker), barium chloride (1 mM, K-IR channel blocker), or glibenclamide (10 mu M, K-ATP channel blocker). Moreover, pretreatment with tiliacorinine 12'-O-acetate reduced the effect of L-NAME (100 mu M) on acetylcholine-induced vasorelaxation. Tiliacorinine 12'O- acetate showed inhibitory effects on CaCl2-induced contracted rings and reduced the contraction induced by phenylephrine (10 mu M) 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.