Summary

Microvascular permeability is increased in pre-eclampsia and may well play an important role in the pathophysiology of the disease. Abnormal transvascular flux of fluid and proteins resulting in tissue edema and dysfunction accounts for some of the clinical manifestations and complications of the disease. Although changes in oncotic pressure gradient resulting from a failure of the interstitial edema preventing mechanisms may contribute to the tissue edema in pre-eclampsia, it is likely that loss of endothelial barrier function due to generalized endothelial dysfunction plays a role in the significantly increased transvascular fluid flux. It is apparent that factor(s) present in the maternal circulation, such as cytokines and growth factors, as well as oxidants released from activated neutrophils, may play a role in the loss of endothelial barrier function in pregnancies complicated by the disease. However, the mechanism(s) of increased microvascular permeability remain unexplained.

Glossary

Filtration capacity: An index of microvascular permeability; reflects the product of the area available for fluid filtration and the permeability per unit surface area.

Osmotic reflection coefficient (a): An index of the microvascular permeability to plasma proteins. a =1.0 means the microvascular surface interface is wholly impermeable to the plasma protein under consideration, a situation rarely encountered in vivo. Values less than 1 imply less complete rejection of the solute

Pre-eclampsia: A hypertensive disorder of pregnancy diagnosed as hypertension (BP of 140/90 or higher) and proteinuria (24 hours urine protein of 0.3 g/L or higher) occurring for the first time after 20 weeks gestation, and reversal of both after delivery.

Bibliography

Anim-Nyame, N., Gamble, J., Sooranna, S. R., Johnson, M. R., and Steer, P. J. (2003). Microvascular permeability is related to circulating levels of TNF-a in pre-eclampsia. Cardiovasc. Res. 58(1), 162-169. This article provides evidence that microvascular permeability in pre-eclampsia correlates with circulating levels of TNF-a but not VEGF.

Bates, D. O., Lodwick, D., and Williams, B. (1999). Vascular endothelial growth factor and microvascular permeability. Microcirculation 6(2), 83-96. A review of the mechanisms by which VEGF increases microvascular permeability.

Haller, H., Hempel, A., Homuth, V., Mandelkow, A., Busjahn, A., Maasch, C., Drab, M., Lindschau, C., Jupner, A., Vetter K., Dudenhausen, J., and Luft, F. C. (1998). Endothelial-cell permeability and protein kinase C in pre-eclampsia. Lancet 3 51, 945-949. This article provided evidence for the first time that a factor(s) present in the sera of women with pre-eclampsia increased microvascular permeability. Redman, C. W., Sacks, G. P., and Sargent, I. L. (1999). Pre-eclampsia: An excessive maternal inflammatory response to pregnancy. Am. J. Obstet. Gynecol. 180, 499-506. A detailed review of the evidence that the endothelial dysfunction of pre-eclampsia is part of a generalized inflammatory response that is common to pregnancy but exaggerated in pregnancies complicated by the disease. Yuan, S. Y. (2003). Protein kinase signalling in the modulation of microvascular permeability. Vasc. Pharmacol. 39, 213-223. A review of the complex interactions between signaling molecules and structural proteins that influence endothelial barrier integrity.

Capsule Biography

Dr. Nick Anim-Nyame is an obstetrician with a research interest in microvascular physiology. He was winner of the Burroughs Wellcome prize at the summer 2000 FASEB Conference and of the European Microcirculation Society travel award (2001). His current research interests are regulation of microvascular blood flow, particularly mechanisms for sensing tissue hypoxia, and microvascular changes in complicated pregnancies.

Dr. John Gamble pioneered the plethysmographic system for noninva-sive assessment of microvascular permeability and other microvascular parameters in humans. He is currently honorary Senior Research Fellow at the School of Sports and Exercise Sciences. University of Birmingham, United Kingdom.

Professor Philip J. Steer is Academic Head of Obstetrics and Gynaecology at Chelsea and Westminster Hospital, London. He is a member of the editorial board of The British Journal of Obstetrics & Gynaecology and was president of the British Association of Perinatal Medicine. His current research interest is maternal factors affecting fetal growth.

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