Effect of Vascular Endothelial Growth Factor (VEGF) on microcirculatory water and protein flux in the rat intestine

Vascular endothelial growth factor(VEGF), a dimeric glycoprotein angiogenic cytokine, was originally described as Vascular Permeability Factor (VPF) because of its potent enhancement of local microvascular fluid leakage. To further elucidate the underlying mechanism and relative participation of enhanced permeability(P) vs. increased capillary filtering surface area (S) in raising the PS product, we examined changes in transvascular water and protein movement by serially determining lymph flow and total protein concentration (refractometry) in anesthetized Sprague-Dawley rats with indwelling intestinal lymphatic cannulae before and for 120 minutes after a single IV dose of 100 μg recombinant human VEGF-1 and compared the findings to control rats. Microcirculatory fluxes were determined by the volume of lymph in serial 10 min collections (water flux or WF in μl/10 min) and the protein flux (PF in μg/10 min) calculated as WF x total protein content in μg/μl. Results: Table (Mean±SEM): Group (n) Flux 0 min 30 min 60 min 90 min VEGF (3) WF 42.3±18.9 160±44.2 67.7±17.5 47.0±15.5 PF 1106±367 4571±431 1727±202 1306±283 Controls (3) WF 36.0±0.6 26.0±3.2 25.7±1.5 12.0±4.6 PF 768±381 619±255 688±222 460±246 VEGF promptly increased WF, which reached 310% of the baseline value (p<0.02) by 30 min and declined steadily thereafter. PF showed a similar response. VEGF effect was rapidly reversible with maintenance of intestinal blood capillary integrity (single observation of prompt lymph protein dilution or "washdown" after superior mesenteric venous constriction). Thus, VEGF, like cytokines IL-2 and TNF, appears to exert its microcirculatory action by enhancing capillary filtering surface area (S), thereby raising the PS product and promoting transvascular movement of both water and protein.