Openings in frog microvascular endothelium induced by high intravascular pressures.

1. We have investigated the effects of microvascular pressures, high enough to rupture the vessel wall, upon the ultrastructure and permeability of mesenteric capillaries in pithed frogs. 2. The vessels were perfused via micropipettes with Ringer solutions containing bovine serum albumin (1 mg ml-1) and a few human red cells. After a perfused section of vessel had been closed downstream, pressure (applied via the micropipette) was raised in a series of steps of 10 mmHg, each lasting approximately 10 s, until the vessel ruptured. Fluid filtration through the vessel wall prior to rupture was estimated from the movements of the red cells. 3. Seven vessels were fixed in glutaraldehyde immediately after rupture and prepared for electron microscopy. The electron micrographs revealed openings in the vessel walls and thirty-six of these gaps were completely defined in runs of serial sections made on four of the vessels. Twenty-nine of these gaps passed through the endothelial cells (transcellular) and seven were intercellular. 4. The pressure at which a vessel ruptured, Pb, was measured in twenty-nine vessels and had a mean +/- S.E.M. value of 79.6 +/- 5.0 cmH2O. In ten of these vessels, which had a mean +/- S.E.M. Pb of 84.2 +/- 6.5 cmH2O, microvascular pressure was lowered immediately after the initial rupture and the vessel perfused at a pressure of 20 cmH2O. Pb was then remeasured and found to be 69.9 +/- 8.4 cmH2O, which was not significantly different from its initial value. 5. Hydraulic permeability (Lp) was measured in six vessels over the range of 15-30 cmH2O before and 10 min after the vessel wall ruptured at high pressure. Mean values were 5.5 x 10(-7) and 4.0 x 10(-7) cms-1 cmH2O-1 and were not significantly different. 6. At pressures equal to and 10 mmHg below Pb, small short-lived increases in filtration rate were observed. It is suggested that these may correspond to the increased permeability to fluid and macromolecules observed at high microvascular pressures in intact capillary beds.