Anemoside A3-induced Relaxation in Rat Renal Arteries: Role of Endothelium and Ca2+ Channel Inhibition

Anemoside A(3), a lupane-type triterpenoid saponin, exists in the roots of Pulsatilla chinensis, but its pharmacological properties are largely unknown. The present study aimed to investigate the mechanisms underlying anemoside A(3)-induced relaxation in rat renal arteries. Changes of isometric force were determined on arteries with a myograph. Anemoside A(3) caused concentration-dependent relaxation in precontracted aortas, mesenteric, left coronary, and renal arteries. Removal of endothelium or treatment with charybdotoxin plus apamin slightly but significantly attenuated the relaxation in renal arteries. TEA(+) inhibited the relaxation caused by anemoside A(3) in renal arteries with and without endothelium while glibenclamide, BaCl2, or capsaicin had no effect on it. Anemoside A(3) produced less relaxation in rings contracted by 60mM KCl compared with rings contracted by receptor-dependent constrictors. It further 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 A(3)-induced relaxation. Taken together, the present results indicate that anemoside A(3) 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.