VEGF and ATP act by different mechanisms to increase microvascular permeability and endothelial [Ca2+](i)

T. M. Pocock, B. Williams, F. E. Curry, D. O. Bates

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

Vascular endothelial growth factor (VEGF) increases hydraulic conductivity (L(p)) by stimulating Ca2+ influx into endothelial cells. To determine whether VEGF-mediated Ca2+ influx is stimulated by release of Ca2+ from intracellular stores, we measured the effect of Ca2+ store depletion on VEGF-mediated increased L(p) and endothelial intracellular Ca2+ concentration ([Ca2+](i)) of frog mesenteric microvessels. Inhibition of Ca2+ influx by perfusion with NiCl2 significantly attenuated VEGF-mediated increased [Ca2+](i). Depletion of Ca2+ stores by perfusion of vessels with thapsigargin did not affect the VEGF-mediated increased [Ca2+](i) or the increase in L(p). In contrast, ATP-mediated increases in both [Ca2+](i) and L(p) were inhibited by thapsigargin perfusion, demonstrating that ATP stimulated store-mediated Ca2+ influx. VEGF also increased Mn2+ influx after perfusion with thapsigargin, whereas ATP did not. These data showed that VEGF increased [Ca2+](i) and L(p) even when Ca2+ stores were depleted and under conditions that prevented ATP-mediated increases in [Ca2+](i) and L(p). This suggests that VEGF acts through a Ca2+ store-independent mechanism, whereas ATP acts through Ca2+ store-mediated Ca2+ influx.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume279
Issue number4 48-4
StatePublished - 2000

Keywords

  • Adenosine 5'-triphosphate
  • Calcium stores
  • Endothelial calcium
  • Intracellular calcium concentration
  • Vascular endothelial growth factor
  • Vascular permeability

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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