Capillaries, caveolae, calcium and cyclic nucleotides: a new look at microvascular permeability

Over the past 35 years much effort has been directed at identifying the pathways through microvascular endothelium and unravelling the interactions between the convective and diffusive forces which drive fluid and solutes through them. While increases in permeability induced by inflammatory mediators are known to result from the formation of gaps in venular endothelium, it is only recent advances in cell biology that have allowed the mechanisms regulating permeability to be investigated from a sound base. Results from the general biology of vesicular transport have been applied in studies on the caveolae of microvascular endothelium. Work on single perfused microvessels and on endothelial cell cultures have revealed the importance of intracellular Ca2+ and both cAMP and cGMP in regulating permeability. Even the belief that permeability is increased by gaps developing between the cells has been challenged. Although the mechanisms regulating permeability remain far from clear, sensible hypotheses can now be proposed and tested.