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

Abstract

Anemoside A₃, 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 A₃-induced relaxation in rat renal arteries. Changes of isometric force were determined on arteries with a myograph. Anemoside A₃ 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 A₃ in renal arteries with and without endothelium while glibenclamide, BaCl₂, or capsaicin had no effect on it. Anemoside A₃ produced less relaxation in rings contracted by 60 mM 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 A₃-induced relaxation. 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.

Pulsatilla chinensis - Ranunculaceae - anemoside A₃ - vasorelaxation - Ca²⁺ channel - endothelium - rat renal arteries

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1 DMZ and SML contributed equally.