Brazilin isolated from the heartwood of Caesalpinia sappan L induces endothelium-dependent and -independent relaxation of rat aortic rings  

作　　者：Yu YAN Yu-cai CHEN Yi-huang LIN Jing GUO Zi-ran NIU Li LI Shou-bao WANG Lian-hua FANG Guan-hua DU 

机构地区：[1]State Key Laboratory of Bioactive Substances and Functions of Natural Medicines [2]Beijing Key Laboratory of Drug Targets Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China

出　　处：《Acta Pharmacologica Sinica》2015年第11期1318-1326,共9页中国药理学报（英文版）

基　　金：Acknowledgements This study was supported by grants from the National Science and Technology Major Project （No 2013ZX09103-001-008 and 2012ZX09103-101-078） and the National Natural Science Foundation of China （No 81102444 and 81202538）.

摘　　要：Aim： Brazilin is one of the major constituents of Caesalpinia sappan L with various biological activities. This study sought to investigate the vasorelaxant effect of brazilin on isolated rat thoracic aorta and explore the underlying mechanisms. methods： Endothelium-intact and -denuded aortic rings were prepared from rats. The tension of the preparations was recorded isometrically with a force displacement transducer connected to a polygraph. The phosphorylation levels of ERK1/2 and myosin light chain （MLC） were analyzed using Western blotting assay. Results： Application of brazilin （10-100 pmol/L） dose-dependently relaxed the NE- or high K^＋-induced sustained contraction of endothelium-intact aortic rings （the ECho was 83.51±5.6 and 79.79±4.57 pmol/L, respectively）. The vasorelaxant effect of brazilin was significantly attenuated by endothelium removal or by pre-incubation with L-NAME, methylene blue or indomethacin. In addition, pre-incubation with brazilin dose-dependently attenuated the vasoconstriction induced by KCI, NE or Ang II. Pre-incubation with brazilin also markedly suppressed the high K^＋-induced extracellular Ca^2＋ influx and NE-induced intracellular Ca^2＋ release in endothelium- denuded aortic rings. Pre-incubation with brazilin dose-dependently inhibited the NE-stimulated phosphorylation of ERK1/2 and MLC in both endothelium-intact and -denuded aortic rings. Conclusion： Brazilin induces relaxation in rat aortic rings via both endothelium-dependent and -independent ways as well as inhibiting NE-stimulated phosphorylation of ERK1/2 and MLC. Brazilin also attenuates vasoconstriction via blocking voltage- and receptor- operated Ca^2＋ channels.Aim： Brazilin is one of the major constituents of Caesalpinia sappan L with various biological activities. This study sought to investigate the vasorelaxant effect of brazilin on isolated rat thoracic aorta and explore the underlying mechanisms. methods： Endothelium-intact and -denuded aortic rings were prepared from rats. The tension of the preparations was recorded isometrically with a force displacement transducer connected to a polygraph. The phosphorylation levels of ERK1/2 and myosin light chain （MLC） were analyzed using Western blotting assay. Results： Application of brazilin （10-100 pmol/L） dose-dependently relaxed the NE- or high K^＋-induced sustained contraction of endothelium-intact aortic rings （the ECho was 83.51±5.6 and 79.79±4.57 pmol/L, respectively）. The vasorelaxant effect of brazilin was significantly attenuated by endothelium removal or by pre-incubation with L-NAME, methylene blue or indomethacin. In addition, pre-incubation with brazilin dose-dependently attenuated the vasoconstriction induced by KCI, NE or Ang II. Pre-incubation with brazilin also markedly suppressed the high K^＋-induced extracellular Ca^2＋ influx and NE-induced intracellular Ca^2＋ release in endothelium- denuded aortic rings. Pre-incubation with brazilin dose-dependently inhibited the NE-stimulated phosphorylation of ERK1/2 and MLC in both endothelium-intact and -denuded aortic rings. Conclusion： Brazilin induces relaxation in rat aortic rings via both endothelium-dependent and -independent ways as well as inhibiting NE-stimulated phosphorylation of ERK1/2 and MLC. Brazilin also attenuates vasoconstriction via blocking voltage- and receptor- operated Ca^2＋ channels.

关 键 词：BRAZILIN rat aortic rings VASORELAXATION ENDOTHELIUM nitric oxide calcium channels ERK1/2 myosin light chain 

分 类 号：Q463[生物学—生理学] TS201.22[轻工技术与工程—食品科学]