Vegf induces no-dependent hyperpermeability in coronary
venules.
Wu, H. Mac, Qiaobing Huang, Yuan Yuan, and Harris J. Granger.
Microcirculation Research Institute and Departments of Medical
Physiology and Surgery, Texas A&M University Health Science Center,
Temple, TX
APStracts 3:0405H, 1996.
The purpose of this study was to investigate the direct effect of
vascular endothelial growth factor (VEGF) on microvascular
permeability and its signaling mechanisms. The apparent permeability
coefficient to albumin was measured in isolated coronary venules.
Topical application of VEGF dose-dependently and transiently
increased the albumin permeability by two- to three-fold. Inhibition
of nitric oxide (NO) synthesis with NG-monomethyl-L-arginine
abolished VEGF-induced venular hyperpermeability. Furthermore,
because NO exerts vasoactive effects through stimulation of guanylate
cyclase (GC) and the subsequent production of cyclic GMP (cGMP), we
examined the role of GC and cGMP-dependent protein kinase (PKG) in
mediation of VEGF s action. The permeability response to VEGF was
measured in the presence of the selective GC inhibitor 1H-[1.2.4]
oxadiazolo[4,3-a]quinoxalin-1-one and the specific PKG inhibitor
KT5823. Both inhibitors reduced basal permeability and prevented the
hyperpermeability response to VEGF. Therefore, we suggest that VEGF
modulates microvascular permeability via a signaling cascade
involving NO synthesis, GC stimulation and PKG activation.
Received 9 August 1996; accepted in final form 5 September 1996.
APS Manuscript Number H729-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 7 October 1996