Differential Effects of Vascular Endothelial Growth Factor-C and Placental Growth Factor-1 on the Hydraulic Conductivity of Frog Mesenteric Capillaries

Abstract

Vascular endothelial growth factors (VEGFs) are known to increase vascular permeability. VEGF-A acts on two receptor tyrosine kinases, VEGF receptor-1 (VEGF-R1 or flt-1) and VEGF receptor-2 (VEGF-R2, flk-1 or KDR). VEGF-C acts only on VEGF-R2 on vascular endothelial cells, whereas placental growth factor-1 (PlGF-1) acts only on VEGF-R1. The effects of perfusion of these receptor-specific proteins on hydraulic conductivity (Lp) was measured in frog mesenteric capillaries. The effect of PlGF on Lp was not conclusive, and overall fluid flux did not increase during that time. VEGF-C acutely and transiently increased Lp (4.5 ± 0.9-fold), which was more obvious in a subset of vessels, in a similar manner to that reported for VEGF-A. In the subset of vessels in which VEGF-C significantly increased Lp acutely, there was a sustained 12-fold increase in Lp 20 min after perfusion, but this was not seen in those vessels which did not respond acutely to VEGF-C, or in vessels exposed to PlGF-1. Lp was also increased 24 h after perfusion with VEGF-C, but not with PlGF-1. Western blot analysis showed that VEGF-R1 and VEGF-R2 are both present in frog tissue. These data show that the VEGFs that stimulate VEGF-R2 chronically increase Lp, but not those that stimulate VEGF-R1 only. This supports the hypothesis that chronic increases in microvascular permeability induced by VEGF are mediated via activation of VEGF-R2 rather than VEGF-R1.