AJP - Heart and Circulatory Physiology, Vol 273, Issue 2 687-H694, Copyright © 1997 by American Physiological Society

ARTICLES

Vascular endothelial growth factor increases microvascular permeability via a Ca(2+)-dependent pathway

D. O. Bates and F. E. Curry
Department of Human Physiology, School of Medicine, University of California, Davis 95616, USA. dob1@le.ac.uk

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.

This article has been cited by other articles:

				H.-W. Cheng, A.F. James, R.R. Foster, J.C. Hancox, and D.O. Bates VEGF Activates Receptor-Operated Cation Channels in Human Microvascular Endothelial Cells Arterioscler. Thromb. Vasc. Biol., August 1, 2006; 26(8): 1768 - 1776. [Abstract] [Full Text] [PDF]

				D. Mehta and A. B. Malik Signaling Mechanisms Regulating Endothelial Permeability Physiol Rev, January 1, 2006; 86(1): 279 - 367. [Abstract] [Full Text] [PDF]

				C. J. Gore, W. G. Hopkins, and C. M. Burge Errors of measurement for blood volume parameters: a meta-analysis J Appl Physiol, November 1, 2005; 99(5): 1745 - 1758. [Abstract] [Full Text] [PDF]

				F. L. Minnear, L. Zhu, and P. He Sphingosine 1-phosphate prevents platelet-activating factor-induced increase in hydraulic conductivity in rat mesenteric venules: pertussis toxin sensitive Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H840 - H844. [Abstract] [Full Text] [PDF]

				L. Zhu and P. He Platelet-activating factor increases endothelial [Ca2+]i and NO production in individually perfused intact microvessels Am J Physiol Heart Circ Physiol, June 1, 2005; 288(6): H2869 - H2877. [Abstract] [Full Text] [PDF]

				C. A. Glass, T. M. Pocock, F. E. Curry, and D. O. Bates Cytosolic Ca2+ concentration and rate of increase of the cytosolic Ca2+ concentration in the regulation of vascular permeability in Rana in vivo J. Physiol., May 1, 2005; 564(3): 817 - 827. [Abstract] [Full Text] [PDF]

				T.-G. Cui, R. R. Foster, M. Saleem, P. W. Mathieson, D. A. Gillatt, D. O. Bates, and S. J. Harper Differentiated human podocytes endogenously express an inhibitory isoform of vascular endothelial growth factor (VEGF165b) mRNA and protein Am J Physiol Renal Physiol, April 1, 2004; 286(4): F767 - F773. [Abstract] [Full Text] [PDF]

				T. M. Pocock, R. R. Foster, and D. O. Bates Evidence of a role for TRPC channels in VEGF-mediated increased vascular permeability in vivo Am J Physiol Heart Circ Physiol, March 1, 2004; 286(3): H1015 - H1026. [Abstract] [Full Text] [PDF]

				R. R. Foster, R. Hole, K. Anderson, S. C. Satchell, R. J. Coward, P. W. Mathieson, D. A. Gillatt, M. A. Saleem, D. O. Bates, and S. J. Harper Functional evidence that vascular endothelial growth factor may act as an autocrine factor on human podocytes Am J Physiol Renal Physiol, June 1, 2003; 284(6): F1263 - F1273. [Abstract] [Full Text] [PDF]

				C. A. Glass and D. O. Bates Role of endothelial Ca2+ stores in the regulation of hydraulic conductivity of Rana microvessels in vivo Am J Physiol Heart Circ Physiol, April 1, 2003; 284(4): H1468 - H1478. [Abstract] [Full Text] [PDF]

				F. Wang, K. G. Rendahl, W. C. Manning, D. Quiroz, M. Coyne, and S. S. Miller AAV-Mediated Expression of Vascular Endothelial Growth Factor Induces Choroidal Neovascularization in Rat Invest. Ophthalmol. Vis. Sci., February 1, 2003; 44(2): 781 - 790. [Abstract] [Full Text] [PDF]

				N. Ferrara Role of vascular endothelial growth factor in regulation of physiological angiogenesis Am J Physiol Cell Physiol, June 1, 2001; 280(6): C1358 - C1366. [Abstract] [Full Text] [PDF]

				T. M. Pocock, B. Williams, F. E. Curry, and D. O. Bates VEGF and ATP act by different mechanisms to increase microvascular permeability and endothelial [Ca2+]i Am J Physiol Heart Circ Physiol, October 1, 2000; 279(4): H1625 - H1634. [Abstract] [Full Text] [PDF]

				I. Zachary, A. Mathur, S. Yla-Herttuala, and J. Martin Vascular Protection : A Novel Nonangiogenic Cardiovascular Role for Vascular Endothelial Growth Factor Arterioscler. Thromb. Vasc. Biol., June 1, 2000; 20(6): 1512 - 1520. [Abstract] [Full Text] [PDF]

				C. C. Michel and F. E. Curry Microvascular Permeability Physiol Rev, July 1, 1999; 79(3): 703 - 761. [Abstract] [Full Text] [PDF]

				W. G. Mayhan VEGF increases permeability of the blood-brain barrier via a nitric oxide synthase/cGMP-dependent pathway Am J Physiol Cell Physiol, May 1, 1999; 276(5): C1148 - C1153. [Abstract] [Full Text] [PDF]

				H. m. Wu, Y. Yuan, D. C. Zawieja, J. Tinsley, and H. J. Granger Role of phospholipase C, protein kinase C, and calcium in VEGF-induced venular hyperpermeability Am J Physiol Heart Circ Physiol, February 1, 1999; 276(2): H535 - H542. [Abstract] [Full Text] [PDF]

				M. Wellner, C. Maasch, C. Kupprion, C. Lindschau, F. C. Luft, and H. Haller The Proliferative Effect of Vascular Endothelial Growth Factor Requires Protein Kinase C-{alpha} and Protein Kinase C-{zeta} Arterioscler. Thromb. Vasc. Biol., January 1, 1999; 19(1): 178 - 185. [Abstract] [Full Text] [PDF]