Normal Endothelium -- Functional Ultrastructure of the Vascular Endothelium: Changes in Various Pathologies -- Development of the Endothelium -- Transport Across the Endothelium: Regulation of Endothelial Permeability -- Calcium Signalling in the Endothelium -- Eicosanoids and the Vascular Endothelium -- Nitric Oxide and the Vascular Endothelium -- Angiotensin, Bradykinin and the Endothelium -- Endothelin -- Transport Across the Endothelium: Regulation of Endothelial Permeability.

It was with great pleasure that I accepted the invitation of Springer to edit this book. My association with the vascular endothelium covers a large part of my scientific career and, as with any good long-standing relationship, it has had moments of great excitement and periods of laborious construction. It has sometimes been difficult but has never given me cause for despondency. Indeed, in the last quarter of a century, research on the vascular endothelium has been very productive and its results have contributed, arguably more than any others, to unravelling the mystery of cardiovascular disease, its origin, its development, its complications and its prevention or treatment once it has developed. I am very happy that Annie Higgs agreed to join me in this task. Over the years we have collaborated closely and, as always, she has shouldered the brunt of the work and has made sure that things get done to everybody{u2019}s satisfaction. We have also been fortunate in that the scientists who have made some of the most significant contributions in the field agreed to write chapters; as a result, we have produced two volumes which is a good representation of our knowledge in early 2006. We are, however, aware that the field has expanded beyond all expectation and that there may have been some oversight in the covering of a specific area or some aspect of it. This is compounded by the speed at which knowledge is being generated, with more than 4,100 papers concerning the endothelium published in 2005. These volumes are organised in such a way that the early chapters discuss the structure, development and function of the normal vascular endothelium. The subsequent chapters consider conditions that lead to disruption of vascular physiology, while the later chapters deal with specific pathologies and their treatment. The final chapter describes various gene-therapy strategies for the treatment of vascular pathologies. Interestingly, although this field of research can now be considered mature, it continues to generate a great deal of new information at a time when some of its fruits are having a direct impact on clinical medicine. This is clearly exemplified in the contents of most of the chapters. The concept of endothelial dysfunction, although mooted many years ago, has come to the fore and has been very useful in defining a situation which may exist long before the overt signs of vascular diseases can be identified. Although VI Preface endothelial dysfunction is likely to comprise a variety of disturbances, it is interesting that these days it is almost exclusively measured as a decrease in nitric oxide (NO)-dependent vascular dilatation, either induced by suitable pharmacological agonists or by increases in blood flow. Oxidative stress, which is associated with the genesis of endothelial dysfunction, is a loose term used to define an imbalance between the release of oxygen-derived free radicals and the anti-oxidant systems of the body. Many years ago our work established that reactive oxygen species are important in reducing the local concentrations of both prostacyclin and NO. It is now clear that free radicals also affect other homeostatic systems in the vasculature. However, many things remain to be clarified, especially the origin of oxidative stress in early disease