Plasma from women with severe pre-eclampsia increases microvascular permeability in an animal model in vivo.
Pre-eclampsia results in oedema, hypertension and proteinuria, and is associated with increased vascular permeability. A number of studies have pointed to the existence of a circulating macromolecule that induces this endothelial dysfunction. To test whether this circulating factor could increase vascular permeability, we have measured the effect of dialysed human plasma from pregnant women with mild or severe pre-eclampsia (pre-eclamptic toxaemia). Plasma was collected from patients with mild or severe pre-eclampsia and from normotensive women. Plasma was dialysed against frog Ringer's solution using a 12-14 kDa molecular-mass cut-off dialysis tubing. pi c (colloid osmotic pressure) was measured with a modified Hansen oncometer. Lp (hydraulic conductivity) and sigma (oncotic reflection coefficient) were measured in individually perfused frog mesenteric microvessels using the Landis-Michel technique during perfusion with dialysed plasma. Perfusion of vessels with normal plasma or plasma from patients with mild pre-eclampsia did not alter either Lp or sigma. However, plasma from patients with severe pre-eclampsia resulted in a 3.8+/-0.3-fold increase in Lp and a reduction in sigma from 0.96+/-0.03 to 0.80+/-0.11. There was a significant correlation between the change in sigma and the change in Lp, suggesting that the increase in permeability was due to an increase in pore size in these vessels. A circulating macromolecule in human plasma in severe pre-eclampsia is therefore able to increase vascular permeability in an animal model. The nature of the circulating macromolecule is not known, except that it is, or is bound to, a molecule greater than 12 kDa.
Neal
Christopher R
CR
Microvascular Research Laboratories, Department of Physiology, Preclinical Veterinary School, University of Bristol, Bristol, BS2 8EJ, UK.
Hunter
Alyson J
AJ
Harper
Steven J
SJ
Soothill
Peter W
PW
Bates
David O
DO
D000818:Animals; D002199:Capillary Permeability; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D023421:Models, Animal; D009997:Osmotic Pressure; D010949:Plasma; D011225:Pre-Eclampsia / Q000097:blood*; D011247:Pregnancy; D011896:Rana temporaria; D018709:Statistics, Nonparametric