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


METHODS
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).


RESULTS
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 EC50values 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+(BKCa) 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.


CONCLUSIONS
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.
Department of Radiation Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China.|Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou 730000, China.|Key Laboratory of Basic Research of Heavy Ion Radiation Application in Medicine of Gansu Province, Lanzhou 730000, China.
Lu
L
Gan
Center of Mitochondria and Healthy Aging, School of Life Sciences, Yantai University, Yantai 264000, China.
Zhen-Hua
ZH
Wang
Department of Radiation Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China.|Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou 730000, China.|Key Laboratory of Basic Research of Heavy Ion Radiation Application in Medicine of Gansu Province, Lanzhou 730000, China.
Hong
H
Zhang
Department of Radiation Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China.|Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou 730000, China.|Key Laboratory of Basic Research of Heavy Ion Radiation Application in Medicine of Gansu Province, Lanzhou 730000, China.
Xin
X
Zhou
Key Laboratory of Xinjiang Endemic Phytomedicine Resources, School of Pharmacy, Shihezi University, Shihezi 832002, China.
Hui
H
Zhou
Department of Radiation Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China.|Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou 730000, China.|Key Laboratory of Basic Research of Heavy Ion Radiation Application in Medicine of Gansu Province, Lanzhou 730000, China.
Chao
C
Sun
Department of Radiation Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China.|Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou 730000, China.|Key Laboratory of Basic Research of Heavy Ion Radiation Application in Medicine of Gansu Province, Lanzhou 730000, China.
Jing
J
Si
Department of Radiation Medicine, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000, China.|Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Lanzhou 730000, China.|Key Laboratory of Basic Research of Heavy Ion Radiation Application in Medicine of Gansu Province, Lanzhou 730000, China.
Rong
R
Zhou
Center of Mitochondria and Healthy Aging, School of Life Sciences, Yantai University, Yantai 264000, China.
Cheng-Jun
CJ
Ma
Center of Mitochondria and Healthy Aging, School of Life Sciences, Yantai University, Yantai 264000, China.
Ji
J
Li
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology*; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000037:antagonists & inhibitors; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012502:Sapogenins / Q000494:pharmacology*; D013237:Stereoisomerism; D014665:Vasodilator Agents / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D053496:Inositol 1,4,5-Trisphosphate Receptors; D012502:Sapogenins; D014665:Vasodilator Agents; C062916:protopanaxadiol; D002118:Calcium