The chronic effect of vascular endothelial growth factor on individually perfused frog mesenteric microvessels.
1. Hydraulic conductivity (Lp) of the wall of perfused microvessels has previously been shown to be chronically increased 24 h after a 10 min perfusion with vascular endothelial growth factor (VEGF). In order to investigate this further, Lp and the effective oncotic pressure difference (f3DeltaPi) acting across the vessel walls was measured before exposure to VEGF and 24 h later after the mesentery had been replaced in the abdominal cavity. 2. Acute 10 min perfusion with VEGF did not chronically change f3DeltaPi despite chronically increasing Lp 6.8 +/- 1.2-fold. This suggests that pathways formed 24 h after perfusion with VEGF which increase hydraulic conductivity of the capillary walls have the same reflection coefficient as those present before VEGF. 3. Acute 10 min perfusion with VEGF significantly increased the diameter of vessels after 24 h by 48 +/- 13%. To determine whether this was due to changes in the compliance of the vessel wall, the distensibility of microvessels was measured before and 24 h after perfusion with VEGF. The distensibility was increased 45 +/- 15% by VEGF but this was not great enough to account for the increase in diameter. 4. The chronic increase in Lp could be attenuated by inhibition of nitric oxide synthase with L-NAME. In addition, the chronic increase in permeability was correlated with the acute response to VEGF (r = 0.71, P < 0.01) suggesting that the acute and chronic changes may be related. 5. These results show that VEGF chronically increases Lp without affecting the oncotic reflection coefficient. This may be due to reduced pore path length, or increased small pore numbers, which are properties of fenestrated capillaries. They also show that VEGF increases microvascular distensibility and diameter.
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Cardiovascular Research Institute, University of Leicester, Leicester, UK. dob1@le.ac.uk
D000465:Algorithms; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002196:Capillaries / Q000187:drug effects; D016228:Endothelial Growth Factors / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008222:Lymphokines / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052250:Nitric Oxide Synthase Type III; D009994:Osmolar Concentration; D010477:Perfusion; D011896:Rana temporaria; D013152:Splanchnic Circulation / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D004791:Enzyme Inhibitors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D001120:Arginine; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D019331:NG-Nitroarginine Methyl Ester