title: Brazilin isolated from the heartwood of Caesalpinia sappan L induces endothelium-dependent and -independent relaxation of rat aortic rings.
abstract: OBJECTIVE
  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 μmol/L) dose-dependently relaxed the NE- or high K(+)-induced sustained contraction of endothelium-intact aortic rings (the EC50 was 83.51±5.6 and 79.79±4.57 μmol/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 KCl, 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Beijing 100050, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yan
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Beijing 100050, China.
authors.forename: Yu-cai
authors.initials: YC
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Beijing 100050, China.
authors.forename: Yi-huang
authors.initials: YH
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Beijing 100050, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Beijing 100050, China.
authors.forename: Zi-ran
authors.initials: ZR
authors.lastname: Niu
authors.affiliation: 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.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Shou-bao
authors.initials: SB
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Beijing 100050, China.
authors.forename: Lian-hua
authors.initials: LH
authors.lastname: Fang
authors.affiliation: 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.
authors.forename: Guan-hua
authors.initials: GH
authors.lastname: Du
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000502:physiology; D001578:Benzopyrans / Q000302:isolation & purification / Q000494:pharmacology*; D029911:Caesalpinia / Q000737:chemistry; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D008297:Male; D018994:Myosin Light Chains / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D001578:Benzopyrans; D018994:Myosin Light Chains; D014665:Vasodilator Agents; D019001:Nitric Oxide Synthase; D048049:Extracellular Signal-Regulated MAP Kinases; C044362:brazilin; D019331:NG-Nitroarginine Methyl Ester