Effects of VEGF on Ca^<2+>-Transient in Cultured Lymphatic Endothelial Cells and Mechanical Activity of Isolated Lymph Vessels

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Abstract

We investigated the effects of vascular endothelial growth factor (VEGF<sub>165</sub>) on [Ca<sup>2+</sup>]<sub>i</sub>-transient in cultured lymphatic endothelial cells (LEC) and mechanical activity of isolated dog thoracic ducts. VEGF (0.1-10 ng/ml) caused a dose-dependent increase of the [Ca<sup>2+</sup>]<sub>i</sub> in LEC. Pretreatment with 10<sup>−5 </sup>m genistein or 5×10<sup>−6 </sup>m herbimycin A produced a significant reduction of the VEGF-induced [Ca<sup>2+</sup>]<sub>i</sub>-transient. In the presence of 10<sup>−6 </sup>m thapsigargin, VEGF caused no significant effect on the [Ca<sup>2+</sup>]<sub>i</sub>-transient. Pretreatment with Ca<sup>2+</sup>-free solution containing 0.1 mm EGTA produced no significant effect on the peak increase of [Ca<sup>2</sup>]<sub>i</sub> induced by 0.1 or 10 ng/ml VEGF, but significantly depressed the sustained part of [Ca<sup>2+</sup>]<sub>i</sub> observed at the higher concentration of VEGF. The VEGF (0.1-10 ng/ml) caused a significant dilation of the isolated lymph vessels with intact endothelium, which were precontracted with U46,619. The 10 ng/ml VEGF-induced dilation was significantly reduced by 3×10<sup>−5 </sup>m N<sup>ω</sup>-nitro-l-arginine methyl ester (l-NAME). The action of l-NAME was inhibited by the simultaneous application of 10<sup>−3 </sup>m l-arginine. Mechanical rubbing of the endothelium also caused significant inhibition of the VEGF-induced dilation. The findings suggest that VEGF<sub>165</sub> may activate the receptor-related tyrosine kinase and cause the release of Ca<sup>2+</sup> from the inositol 1,4,5-triphosphate-sensitive intracellular Ca<sup>2+</sup> stores in LEC. VEGF<sub>165</sub> also produces endothelium-dependent nitric oxide-mediated dilation of the precontracted isolated lymph vessels.<br>

Journal

  • The Japanese Journal of Physiology

    The Japanese Journal of Physiology 50(3), 343-355, 2000-06

    THE PHYSIOLOGICAL SOCIETY OF JAPAN

References:  37

Codes

  • NII Article ID (NAID)
    10008291575
  • NII NACSIS-CAT ID (NCID)
    AA00691224
  • Text Lang
    ENG
  • Article Type
    ART
  • ISSN
    0021521X
  • NDL Article ID
    5525792
  • NDL Source Classification
    ZS8(科学技術--医学--解剖学・生理学・生化学)
  • NDL Call No.
    Z53-D40
  • Data Source
    CJP  NDL  J-STAGE 
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