VASCULAR ENDOTHELIAL GROWTH-FACTOR INCREASES MICROVASCULAR PERMEABILITY VIA A CA2-DEPENDENT PATHWAY()

We tested the hypothesis that vascular endothelial growth factor (VEGF ) increases microvascular permeability by increasing calcium influx in to endothelial cells forming the vessel walls. We measured microvessel hydraulic conductivity (L-p) in isolated perfused MS-222-anesthetized frog mesenteric microvessels during perfusion with VEGF under conditi ons that attenuate calcium influx. VEGF increased L-p during a second successive perfusion in the same microvessel by 7.8-fold, which was no t significantly different from that brought about by an initial applic ation of VEGF (5.0-fold). However, under depolarizing conditions, the increase in L-p was reduced from 11.1- to 5.6-fold when depolarized to -10 mV (58 mM K+) and to 2.8-fold when depolarized to 0 mV (100 mM K). Attenuating calcium influx by the addition of nickel ions resulted in a similar attenuation of the increase in L-p (from 13- to 2.5-fold) . VEGF also increased the intracellular calcium concentration in endot helial cells of perfused microvessels as determined by measurement wit h fura 2. We therefore conclude that VEGF increases L-p by increasing calcium influx.