EFFECTS OF VASCULAR ENDOTHELIAL GROWTH-FACTOR (VEGF) VASCULAR-PERMEABILITY FACTOR (VPF) ON HEMODYNAMICS AND PERMSELECTIVITY OF THE ISOLATED-PERFUSED RAT-KIDNEY

Background. Vascular endothelial growth factor (VEGF) or vascular perm eability factor (VPF) is a selective mitogen for endothelial cells; it increases microvascular permeability and has been shown to relax isol ated canine coronary arteries by an endothelium-dependent mechanism. I n many tissues VEGF/VPF is expressed after an appropriate stimulus, mo stly hypoxia. In the kidney VEGF/VPF is constitutively expressed in gl omerular podocytes and epithelia of collecting duct. Glomerular and pe ritubular capillary endothelia also constitutively express specific VE GF receptors. The in vivo function of renal VEGF/VPF is unknown.Method . In the present study the effects of human recombinant VEGF(165), on renal haemodynamics and glomerular permselectivity was investigated in the isolated perfused kidney of the rat. Results. In kidneys preconst ricted by noradrenaline (NA 1.5x10(-7) mol/l) VEGF/VPF (155 pmol/l) ca used an almost complete return of renal perfusion flow rate to pre-NA values (before NA 113+/-4%, after NA 100%, 15 min with VEGF/VPF 111+/- 4%). Shortly after VEGF/VPF administration VEGF/VPF-induced relaxation commenced, and became significant after 2 min (15 min with VEGF/VPF v s without VEGF/VPF 111+/-4% vs 103+/-2%; P < 0.05). In the presence of the NO-synthase inhibitor N-w-nitro-L-arginine (L-NNA; 5 x 10(-5) mol /l) VEGF/VPF caused only small, transient relaxations (before NNA 109/-5%, after NNA 100%, 15 min with VEGF 95+/-2%). The cyclooxygenase in hibitor diclofenac failed to inhibit the relaxing activity of VEGF/VPF (before NA 119+/-4%, after NA+diclofenac 100%, 15 min with VEGF/VPF 1 23+/-5%). VEGF demonstrated no significant increase in renal protein e xcretion rate (after NA pretreatment (=100%): 12.5 min with VEGF/VPF v s without VEGF/VPF: 119+/-10% vs 132+/-11%, n.s.) (after NNA pretreatm ent (=100%) 12.5 min with VEGF/VPF vs without VEGF/VPF 94+/-5% vs 96+/ -4%; n.s.) or clearance quotient of albumin. Glomerular filtration rat e was not influenced by VEGF/VPF in kidneys pretreated with NA (before NA 105+/-5%, after NA 100%, 12.5 min with VEGF/VPF 94+/-2%) or with N NA (before NNA 107+/-6%, after NNA 100%, 12.5 min with VEGF/VPF 96+/-2 %). Fractional glucose and fractional sodium excretion showed flow-dep endent changes. Conclusion. VEGF/VPF can contribute to the relaxing ca pacity of the renal vasculature. This relaxation is partly mediated by the NO/endothelium-derived relaxing factor (EDRF) pathway. In the iso lated perfused rat kidney the glomerular permeability for albumin is n ot affected by VEGF/VPF.