Enhanced local production of vascular endothelial growth factor is not sufficient to increase peritoneal permeability to protein during acute peritonitis

Dialysate concentrations of inflammatory mediators and growth factors, such as vascular endothelial growth factor (VEGF), are increased during acute peritonitis in peritoneal dialysis patients; however, it can be difficult to determine whether these high concentrations are caused by either increased peritoneal permeability or enhanced local production within peritoneal tissues. VEGF and total protein kinetics were first compared in a rabbit model during an 8-h dwell of dialysis solution containing 2.5% dextrose with (peritonitis) and without (control) the addition of 1-2 x 10(5) colony forming units (cfus) of Escherichia coli (series 1 experiments). Series 2 experiments determined whether intraperitoneal administration of indomethacin (75 microg/mL) altered the kinetics of VEGF and its local production during peritonitis. Series 1 experiments showed that peritonitis resulted in increased peritoneal permeability to total protein, enhanced appearance of VEGF in the dialysate, and increased tissue VEGF mRNA expression in the cecum and abdominal muscle tissues. Series 2 experiments showed that intraperitoneal administration of indomethacin during peritonitis blocked the increase in peritoneal permeability to total protein but had no effect on the appearance rate of VEGF in the dialysate. Intraperitoneal indomethacin decreased tissue VEGF mRNA expression in the cecum but not in the diaphragm or abdominal muscle tissues. It is concluded that the enhanced appearance of VEGF in peritoneal dialysate during peritonitis is largely from increased local production within peritoneal tissues. These observations also demonstrate that enhanced local production of VEGF is not sufficient to increase peritoneal permeability to total protein during peritonitis.