Study On The Effect And Mechanism Of Anemoside A₃-induced Relaxation In Rat Renal Arteries

Anemoside A3, a lupane-type pentacyclic triterpenoid saponin, was first isolated by our group from the roots of Pulsatilla chinensis which is commonly used to treat amoebic diseases, vaginal trichromoniasis and bacterial infections in Chinese medicinal remedies. Although pharmacological properties of some saponins have been defined, little is known in literature regarding the vascular action of lupane-type saponins and there is no report about that of anemoside A3. The present study characterized the effect of anemoside A3 in rat resistant arteries and the mechanism of this activity.Aim of the study:The present study aimed to evaluate anemoside A3-induced relaxation in renal arteries and investigate the underlying mechanisms.Materials and methods:Changes of isometric force were determined on rat renal arteries in myograph.Results:In endothelium-intact thoracic aorta, middle cerebral artery and renal artery pre-contracted by phe and left coronary artery pre-contracted by U46619, Anemoside A3 was able to induced dose-dependent relaxation. Anemoside A3 caused concentration-dependent relaxation in arteries contracted by U46619, endothelin-1, phenylephrine and KCl. Removal of endothelium or treatment with charybdotoxin plus apamin slightly but significantly attenuated the relaxation. TEA+ inhibited the relaxation to anemoside A3 in arteries with and without endothelium, while glibenclamide, BaCl2, or capsaicin had no effect. Anemoside A3 produced less relaxation in rings contracted by 60 mM KCl compared with rings contracted by receptor-dependent ligands. Anemoside A3 inhibited contractions induced by Ca2+ influx through nifedipine-sensitive voltage-gated Ca2+ channels, nifedipine-insensitive receptor-operated Ca2+ channels and by intracellular Ca2+ release. Pretreatment with nifedipine attenuated anemoside A3-induced relaxation. Conclusions:Taken together, the present results indicate that anemoside A3 produces relaxation in rat renal arteries through multiple mechanisms. The release of CTX/apamin-sensitive endothelium-derived hyperpolarizing factor, stimulation of TEA+-sensitive K+ channel and inhibition of Ca2+ influx jointly contribute to the relaxation.