Endothelium-independent vasorelaxant effect of 20(S)-protopanaxadiol on isolated rat thoracic aorta

Ginsenosides are considered to be the major pharmacologically active ginseng constituents, whereas 20(S)-protopanaxadiol [20(S)-PPD] is the active metabolite of ginsenosides in gut. In this study we investigated the effect of 20(S)-PPD on isolated rat thoracic aortas as well as its vasorelaxant mechanisms.

Aortic rings with or without endothelium were prepared from Wistar rats and suspended in organ-chambers. The changes in tension of the preparations were recorded through isometric transducers connected to a data acquisition system. The aortic rings were precontracted with phenylephrine (PE, 1 μmol/L) or high-K⁺ (80 mmol/L).

Application of 20(S)-PPD (21.5-108.5 μmol/L) caused concentration-dependent vasodilation of endothelium-intact aortic rings precontracted with PE or high-K⁺, which resulted in the EC₅₀ values of 90.4 or 46.5 μmol/L, respectively. The removal of endothelium had no effect on 20(S)-PPD-induced relaxation. The vasorelaxant effect of 20(S)-PPD was also not influenced by the preincubation with β-adrenergic receptor antagonist propranolol, or with ATP-sensitive K⁺ channel blocker glibenclamide, voltage-dependent K⁺ channel blocker 4-AP and inward rectifier K⁺ channel blocker BaCl₂, whereas it was significantly attenuated by the preincubation with Ca²⁺-activated K⁺ (BK_Ca) channel blocker TEA (1 mmol/L). Furthermore, the inhibition of NO synthesis, cGMP and prostacyclin pathways did not affect the vasorelaxant effect of 20(S)-PPD. In Ca²⁺-free solution, 20(S)-PPD (108.5 μmol/L) markedly decreased the extracellular Ca²⁺-induced contraction in aortic rings precontracted with PE or high-K⁺ and reduced PE-induced transient contraction. Voltage-dependent Ca²⁺ channel antagonist nifedipine inhibited PE-induced contraction; further inhibition was observed after the application of receptor-operated Ca²⁺ channel inhibitor SK&F 96365 or 20(S)-PPD.

20(S)-PPD induces vasorelaxation via an endothelium-independent pathway. The inhibition of voltage-dependent Ca²⁺ channels and receptor-operated Ca²⁺ channels and the activation of Ca²⁺-activated K⁺ channels are probably involved in the relaxation.