Vascular endothelial growth factor increases microvascular permeability via a Ca(2+)-dependent pathway.
We tested the hypothesis that vascular endothelial growth factor (VEGF) increases microvascular permeability by increasing calcium influx into endothelial cells forming the vessel walls. We measured microvessel hydraulic conductivity (Lp) in isolated perfused MS-222-anesthetized frog mesenteric microvessels during perfusion with VEGF under conditions that attenuate calcium influx. VEGF increased Lp during a second successive perfusion in the same microvessel by 7.8-fold, which was not significantly different from that brought about by an initial application of VEGF (5.0-fold). However, under depolarizing conditions, the increase in Lp 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 Lp (from 13- to 2.5-fold). VEGF also increased the intracellular calcium concentration in endothelial cells of perfused microvessels as determined by measurement with fura 2. We therefore conclude that VEGF increases Lp by increasing calcium influx.
Bates
D O
DO
Department of Human Physiology, School of Medicine, University of California, Davis 95616, USA. dob1@le.ac.uk
Curry
F E
FE
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002199:Capillary Permeability / Q000187:drug effects*; D004594:Electrophysiology; D016228:Endothelial Growth Factors / Q000032:analysis / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000502:physiology; D007425:Intracellular Membranes / Q000378:metabolism; D008222:Lymphokines / Q000032:analysis / Q000494:pharmacology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009532:Nickel / Q000494:pharmacology; D009994:Osmolar Concentration; D011894:Rana pipiens; D013618:Tachyphylaxis; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D009532:Nickel; D002118:Calcium