VEGF and ATP act by different mechanisms to increase microvascular permeability and endothelial [Ca(2+)](i).
Vascular endothelial growth factor (VEGF) increases hydraulic conductivity (L(p)) by stimulating Ca(2+) influx into endothelial cells. To determine whether VEGF-mediated Ca(2+) influx is stimulated by release of Ca(2+) from intracellular stores, we measured the effect of Ca(2+) store depletion on VEGF-mediated increased L(p) and endothelial intracellular Ca(2+) concentration ([Ca(2+)](i)) of frog mesenteric microvessels. Inhibition of Ca(2+) influx by perfusion with NiCl(2) significantly attenuated VEGF-mediated increased [Ca(2+)](i). Depletion of Ca(2+) stores by perfusion of vessels with thapsigargin did not affect the VEGF-mediated increased [Ca(2+)](i) or the increase in L(p). In contrast, ATP-mediated increases in both [Ca(2+)](i) and L(p) were inhibited by thapsigargin perfusion, demonstrating that ATP stimulated store-mediated Ca(2+) influx. VEGF also increased Mn(2+) influx after perfusion with thapsigargin, whereas ATP did not. These data showed that VEGF increased [Ca(2+)](i) and L(p) even when Ca(2+) stores were depleted and under conditions that prevented ATP-mediated increases in [Ca(2+)](i) and L(p). This suggests that VEGF acts through a Ca(2+) store-independent mechanism, whereas ATP acts through Ca(2+) store-mediated Ca(2+) influx.
Pocock
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TM
Department of Physiology, University of Bristol, Bristol BS2 8EJ, LE2 7LX United Kingdom.
Williams
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B
Curry
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FE
Bates
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DO
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects*; D016228:Endothelial Growth Factors / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007425:Intracellular Membranes / Q000378:metabolism*; D008222:Lymphokines / Q000494:pharmacology*; D008297:Male; D008345:Manganese / Q000378:metabolism; D008833:Microcirculation / Q000187:drug effects; D009532:Nickel / Q000494:pharmacology; D009994:Osmolar Concentration; D011894:Rana pipiens; D011896:Rana temporaria; D013152:Splanchnic Circulation / Q000187:drug effects; D019284:Thapsigargin / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D002121:Calcium Channel Blockers; D016228:Endothelial Growth Factors; D004791:Enzyme Inhibitors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D008345:Manganese; D019284:Thapsigargin; C022838:nickel chloride; D009532:Nickel; D000255:Adenosine Triphosphate; D002118:Calcium