Induction of vasorelaxation through activation of nitric oxide synthase in endothelial cells by brazilin

Chien Ming Hu, Jaw Jou Kang, Chen Chen Lee, Ching Hao Li, Jiunn Wang Liao, Yu Wen Cheng

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

The vasorelaxant activity of Caesalpinia sappan L., a traditional Chinese medicine, and its major component brazilin were investigated in isolated rat aorta and human umbilical vein endothelial cells. In isolated rat aorta, C. sappan L. extract and brazilin relaxed phenylephrine-induced vasocontraction and increased cyclic guanosine 3′,5′-monophosphate (cGMP) content. Induction of vasorelaxation of brazilin was endothelium-dependent and could be markedly blocked by pretreatment with nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine methyl ester (L-NAME); NG-monomethyl-L-arginine acetate (L-NMMA) and guanylyl cyclase inhibitor, methylene blue; 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and nitric oxide (NO) scavenger, hemoglobin. The increasing cGMP content induced by brazilin was also blocked by pretreatment with L-NAME, methylene blue, and the removal of extracellular Ca2+. In human umbilical vein endothelial cells, brazilin dose-dependently induced an increase in NO formation and NOS activity, which were greatly attenuated by either the removal of extracellular Ca2+ or the chelating of intracellular Ca2+ chelator, 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA-AM). Moreover, brazilin dose-dependently induced the influx of extracellular Ca2+ in human umbilical vein endothelial cells. Collectively, these results suggest that brazilin induces vasorelaxation by the increasing intracellular Ca2+ concentration in endothelial cells of blood vessels and hence activating Ca2+/calmodulin-dependent NO synthesis. The NO is released and then transferred into smooth muscle cells to activate guanylyl cyclase and increase cGMP content, resulting in vasorelaxation.

Original languageEnglish
Pages (from-to)37-45
Number of pages9
JournalEuropean Journal of Pharmacology
Volume468
Issue number1
DOIs
Publication statusPublished - May 2 2003
Externally publishedYes

Fingerprint

Vasodilation
Nitric Oxide Synthase
Endothelial Cells
Guanosine Monophosphate
NG-Nitroarginine Methyl Ester
Human Umbilical Vein Endothelial Cells
omega-N-Methylarginine
Nitric Oxide
Guanylate Cyclase
Methylene Blue
Aorta
Caesalpinia
Ethane
Chinese Traditional Medicine
Phenylephrine
Calmodulin
Chelating Agents
brazilin
Vasodilator Agents
Smooth Muscle Myocytes

Keywords

  • Aorta
  • Brazilin
  • Ca influx
  • Caesalpinia sappan L.
  • Endothelial cell
  • Nitric oxide (NO)
  • Nitric oxide synthase (NOS)
  • Vasorelaxation

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Pharmacology

Cite this

Induction of vasorelaxation through activation of nitric oxide synthase in endothelial cells by brazilin. / Hu, Chien Ming; Kang, Jaw Jou; Lee, Chen Chen; Li, Ching Hao; Liao, Jiunn Wang; Cheng, Yu Wen.

In: European Journal of Pharmacology, Vol. 468, No. 1, 02.05.2003, p. 37-45.

Research output: Contribution to journalArticle

Hu, Chien Ming ; Kang, Jaw Jou ; Lee, Chen Chen ; Li, Ching Hao ; Liao, Jiunn Wang ; Cheng, Yu Wen. / Induction of vasorelaxation through activation of nitric oxide synthase in endothelial cells by brazilin. In: European Journal of Pharmacology. 2003 ; Vol. 468, No. 1. pp. 37-45.
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AB - The vasorelaxant activity of Caesalpinia sappan L., a traditional Chinese medicine, and its major component brazilin were investigated in isolated rat aorta and human umbilical vein endothelial cells. In isolated rat aorta, C. sappan L. extract and brazilin relaxed phenylephrine-induced vasocontraction and increased cyclic guanosine 3′,5′-monophosphate (cGMP) content. Induction of vasorelaxation of brazilin was endothelium-dependent and could be markedly blocked by pretreatment with nitric oxide synthase (NOS) inhibitor, NG-nitro-L-arginine methyl ester (L-NAME); NG-monomethyl-L-arginine acetate (L-NMMA) and guanylyl cyclase inhibitor, methylene blue; 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and nitric oxide (NO) scavenger, hemoglobin. The increasing cGMP content induced by brazilin was also blocked by pretreatment with L-NAME, methylene blue, and the removal of extracellular Ca2+. In human umbilical vein endothelial cells, brazilin dose-dependently induced an increase in NO formation and NOS activity, which were greatly attenuated by either the removal of extracellular Ca2+ or the chelating of intracellular Ca2+ chelator, 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA-AM). Moreover, brazilin dose-dependently induced the influx of extracellular Ca2+ in human umbilical vein endothelial cells. Collectively, these results suggest that brazilin induces vasorelaxation by the increasing intracellular Ca2+ concentration in endothelial cells of blood vessels and hence activating Ca2+/calmodulin-dependent NO synthesis. The NO is released and then transferred into smooth muscle cells to activate guanylyl cyclase and increase cGMP content, resulting in vasorelaxation.

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