Increased microvascular resistance to blood flow in the rat hindlimb after perfusion with neuraminidase.

1. The ability of blood to flow through capillaries with diameters smaller than that of erythrocytes and leucocytes has been explained hypothetically on the basis of electrostatic repulsion between vessel walls and circulating cells, but in the absence of in vivo evidence. Following our discovery of extraordinarily high densities of sialic acids on endothelial surfaces, we have now devised experiments to determine to what extent microcirculatory blood flow might depend on these negative charges. 2. Hindlimbs of rats anaesthetized with ether and pentobarbitone were perfused through the femoral artery at constant volume with continuous recording of inflow resistance: first with carotid arterial blood containing continually infused acetylcholine at concentrations which minimized peripheral resistance without affecting heart rate; then for 5 min with buffered saline containing acetylcholine at the same concentration plus neuraminidase (from Vibrio cholerae, at 0.1 mg/ml) to remove endothelial sialic acids (for control experiments without neuraminidase); and then again with acetylcholine-infused carotid blood. 3. As a consequence of the saline perfusion, there was a rapid initial rise and fall of inflow resistance. The subsequent changes in resistance were calculated as the difference between its lowest value in the first 10 min and the value after 60 min. Controls and neuraminidase-perfused groups were compared using the t test for unpaired measurements. 4. In four control experiments inflow resistance decreased by 10-40% (14 +/- 10%, mean +/- S.E.M.). In three experiments with neuraminidase, inflow resistance increased by 24-38% (29 +/- 4%, mean +/- S.E.M.). The difference between the saline and the neuraminidase-perfused groups was significant (P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)