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

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  • Effects of VEGF on Ca2+-Translent in Cultured Lymphatic Endothelial Cells and Mechanical Activity of Isolated Lymph Vessels.
  • Effects of VEGF on Ca 2 Transient in Cultured Lymphatic Endothelial Cells and Mechanical Activity of Isolated Lymph Vessels

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We investigated the effects of vascular endothelial growth factor (VEGF165) on [Ca2+]i-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 [Ca2+]i in LEC. Pretreatment with 10−5 m genistein or 5×10−6 m herbimycin A produced a significant reduction of the VEGF-induced [Ca2+]i-transient. In the presence of 10−6 m thapsigargin, VEGF caused no significant effect on the [Ca2+]i-transient. Pretreatment with Ca2+-free solution containing 0.1 mm EGTA produced no significant effect on the peak increase of [Ca2]i induced by 0.1 or 10 ng/ml VEGF, but significantly depressed the sustained part of [Ca2+]i 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 3×10−5 m Nω-nitro-l-arginine methyl ester (l-NAME). The action of l-NAME was inhibited by the simultaneous application of 10−3 m l-arginine. Mechanical rubbing of the endothelium also caused significant inhibition of the VEGF-induced dilation. The findings suggest that VEGF165 may activate the receptor-related tyrosine kinase and cause the release of Ca2+ from the inositol 1,4,5-triphosphate-sensitive intracellular Ca2+ stores in LEC. VEGF165 also produces endothelium-dependent nitric oxide-mediated dilation of the precontracted isolated lymph vessels.<br>

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