Alpha-naphthoflavone induces vasorelaxation through the induction of extracellular calcium influx and NO formation in endothelium

Yu W. Cheng, Ching H. Li, Chen Chen Lee, Jaw J. Kang

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The effect of α-naphthoflavone (α-NF) on vascular function was studied in isolated ring segments of the rat thoracic aorta and in primary cultures of human umbilical vein endothelial cells (HUVECs). α-NF induced concentration-dependent relaxation of the phenylephrine-pre-contracted aorta endothelium-dependently and -independently at lower and higher concentrations, respectively. The cGMP, but not cAMP, content was increased significantly in α-NF-treated aorta. Pretreatment with Nω-nitro-L- arginine methyl ester (L-NAME) or methylene blue attenuated both α-NF induced vasorelaxation and the increase of cGMP content significantly. The increase of cGMP content induced by α-NF was also inhibited by chelating extracellular Ca2+ with EGTA. These results suggest that the endothelium-dependent vasorelaxation induced by α-NF is mediated most probably through Ca2+-dependent activation of NO synthase and guanylyl cyclase. In HUVECs, α-NF induced concentration-dependent formation of NO and Ca2+ influx. α-NF-induced NO formation was abolished by removal of extracellular Ca2+ and by pretreatment with the Ca2+ channel blockers SKF 96365 and Ni2+, but not by the L-type Ca2+ channel blocker verapamil. The Ca2+ influx, as measured by 45Ca2+ uptake, induced by α-NF was also inhibited by SKF 96365 and Ni2+. Our data imply that α-NF, at lower concentrations, induces endothelium-dependent vasorelaxation by promoting extracellular Ca2+ influx in endothelium and the activation of the NO-cGMP pathway.

Original languageEnglish
Pages (from-to)377-385
Number of pages9
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume368
Issue number5
DOIs
Publication statusPublished - Nov 2003

Keywords

  • Ca
  • Endothelium
  • Naphthoflavone
  • NO

ASJC Scopus subject areas

  • Pharmacology

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