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

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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-precontracted 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 N ω-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.

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This study was supported in part by a grant from the National Science Council, Taiwan.

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  1. Institute of Toxicology, College of Medicine, National Taiwan University, 1 Jen-Ai Road, Section 1, Taipei, Taiwan

    Ching-Hao Li, Chen-Chen Lee & Jaw-Jou Kang

  2. School of Pharmacy, Taipei Medical University, 250 Wu Hsing Street, Taipei, Taiwan

    Yu-Wen Cheng

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Cheng, YW., Li, CH., Lee, CC. et al. Alpha-naphthoflavone induces vasorelaxation through the induction of extracellular calcium influx and NO formation in endothelium. Naunyn-Schmiedeberg's Arch Pharmacol 368, 377–385 (2003). https://doi.org/10.1007/s00210-003-0820-6

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