Neutrophil enhancement of reperfusion-induced capillary fluid filtration associated with hypercholesterolemia

Fluid filtration rate (J(v)/S) from individual mesenteric capillaries in normocholesterolemic and hypercholesterolemic rats was measured before and after 30 min each of ischemia and reperfusion (I/R). The median I/R-induced increase in J(v)/S (I/R vs. baseline) was 44% in normocholesterolemic rats (n = 11) and 97% in hypercholesterolemic rats (n = 11). A positive correlation slope of 0.20% per mg/dl resulted when the percent J(v)/S increase vs. plasma cholesterol concentration (P = 0.02) was plotted, demonstrating that hypercholesterolemia enhances the capillary response to I/R. Because microvascular pressure did not change significantly after I/R in either group of rats, the increments in J(v)/S likely reflect increased capillary permeability. In hypercholesterolemic rats rendered neutropenic with antineutrophil serum, I/R did not elicit a significant increase in J(v)/S, suggesting that activated neutrophils mediate the exaggerated endothelial barrier dysfunction associated with hypercholesterolemia.