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

文献类型：期刊论文

作者Gan, Lu1,2,3; Wang, Zhen-hua4; Zhang, Hong1,2,3; Zhou, Xin1,2,3; Zhou, Hui5; Sun, Chao1,2,3; Si, Jing1,2,3; Zhou, Rong1,2,3; Ma, Cheng-jun4; Li, Ji4
刊名ACTA PHARMACOLOGICA SINICA
出版日期2016-12-01
卷号37页码:1555-1562
关键词Ginsen 20(S)-protopanaxadiol vasorelaxation aortic rings potassium channels calcium channels
ISSN号1671-4083
DOI10.1038/aps.2016.74
英文摘要Aim: 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 mu mol/L) or high-K+ (80 mmol/L). Results: Application of 20(S)-PPD (21.5-108.5 mu mol/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 mu mol/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 beta-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 mu mol/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. Conclusion: 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.
WOS关键词SMOOTH-MUSCLE-CELLS ; BETA-ADRENOCEPTOR ANTAGONISTS ; PHYSIOLOGICAL ROLES ; K+ CHANNELS ; DEPENDENT RELAXATION ; INTESTINAL BACTERIA ; RED GINSENG ; HYPERTENSION ; GINSENOSIDES ; CONTRACTION
资助项目National Natural Science Foundation of China[U1432248] ; National Natural Science Foundation of China[11305226] ; National Natural Science Foundation of China[11405230] ; National Key Projects of Research and Development[2016YFC0904600] ; Taishan Scholar Program of Shandong Province[tshw201502046] ; Western Talent Program of Chinese Academy of Sciences[2013-165] ; Western Talent Program of Chinese Academy of Sciences[Y460030XB0]
WOS研究方向Chemistry ; Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000389704500004
出版者ACTA PHARMACOLOGICA SINICA
资助机构National Natural Science Foundation of China ; National Key Projects of Research and Development ; Taishan Scholar Program of Shandong Province ; Western Talent Program of Chinese Academy of Sciences
源URL[http://119.78.100.186/handle/113462/43874]  
专题中国科学院近代物理研究所
通讯作者Wang, Zhen-hua; Zhang, Hong
作者单位1.Chinese Acad Sci, Inst Modern Phys, Dept Radiat Med, Lanzhou 730000, Peoples R China
2.Chinese Acad Sci, Key Lab Heavy Ion Radiat Biol & Med, Lanzhou 730000, Peoples R China
3.Key Lab Basic Res Heavy Ion Radiat Applicat Med G, Lanzhou 730000, Peoples R China
4.Yantai Univ, Sch Life Sci, Ctr Mitochondria & Hlth Aging, Yantai 264000, Peoples R China
5.Shihezi Univ, Sch Pharm, Key Lab Xinjiang Endem Phytomed Resources, Shihezi 832002, Peoples R China
推荐引用方式
GB/T 7714		 Gan, Lu,Wang, Zhen-hua,Zhang, Hong,et al. Endothelium-independent vasorelaxant effect of 20(S)-protopanaxadiol on isolated rat thoracic aorta[J]. ACTA PHARMACOLOGICA SINICA,2016,37:1555-1562.
APA Gan, Lu.,Wang, Zhen-hua.,Zhang, Hong.,Zhou, Xin.,Zhou, Hui.,...&Li, Ji.(2016).Endothelium-independent vasorelaxant effect of 20(S)-protopanaxadiol on isolated rat thoracic aorta.ACTA PHARMACOLOGICA SINICA,37,1555-1562.
MLA Gan, Lu,et al."Endothelium-independent vasorelaxant effect of 20(S)-protopanaxadiol on isolated rat thoracic aorta".ACTA PHARMACOLOGICA SINICA 37(2016):1555-1562.

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来源：近代物理研究所

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