The advances made in vascular biology in the last 25 years have considerably changed the perception that one could have of the endothelial cells. Once considered as a diffusion barrier preventing the access of the blood cells to the vascular matrix, the endothelium is now recognized as playing a major role in the control of blood fluidity, platelet aggregation, and vascular tone, but also in immunology, inflammation, angiogenesis, and for serving as a metabolizing and an endocrine organ. -- from the preface Cardiovascular diseases, so prevalent in the Western world during the twentieth century, could well become the scourge of the twenty-first century in emerging countries as well as the West. Endothelial dysfunction linked to an imbalance in the synthesis and/or release of contracting and relaxing factors is often evoked to explain the initiation of the cardiovascular pathology or its development and perpetuation. Two decades ago, when nitric oxide was demonstrated to mediate endothelium-dependent relaxations, the vascular world seemed convinced that nitric oxide was the ultimate and sole explanation for such relaxations. However not everyone agreed. EDHF: The Complete Story is the work of two leading researchers who did not accept that simple conclusion, but instead continued to search, along with others, for a deeper understanding of the ways in which endothelial cells communicate with the underlying smooth muscle to signal it to hyperpolarize. Now with most, if not all, of those ways, uncovered, the authors offer this summary as way of bringing closure to the quest. This monograph reports on the work of many researchers. It summarizes the significant recent discoveries concerning endothelium-dependent hyperpolarizations, which are likely to play a much more important role in cardiovascular physiology and pathology than was originally foreseen Extensively illustrated with original diagrams and schematics that su

The advances made in vascular biology in the last 25 years have considerably changed the perception that one could have of the endothelial cells. Once considered as a diffusion barrier preventing the access of the blood cells to the vascular matrix, the endothelium is now recognized as playing a major role in the control of blood fluidity, platelet aggregation, and vascular tone, but also in immunology, inflammation, angiogenesis, and for serving as a metabolizing and an endocrine organ.
-- from the preface
Cardiovascular diseases, so prevalent in the Western world during the twentieth century, could well become the scourge of the twenty-first century in emerging countries as well as the West. Endothelial dysfunction linked to an imbalance in the synthesis and/or release of contracting and relaxing factors is often evoked to explain the initiation of the cardiovascular pathology or its development and perpetuation. Two decades ago, when nitric oxide was demonstrated to mediate endothelium-dependent relaxations, the vascular world seemed convinced that nitric oxide was the ultimate and sole explanation for such relaxations. However not everyone agreed.
EDHF: The Complete Story is the work of two leading researchers who did not accept that simple conclusion, but instead continued to search, along with others, for a deeper understanding of the ways in which endothelial cells communicate with the underlying smooth muscle to signal it to hyperpolarize. Now with most, if not all, of those ways, uncovered, the authors offer this summary as way of bringing closure to the quest.
This monograph reports on the work of many researchers. It summarizes the significant recent discoveries concerning endothelium-dependent hyperpolarizations, which are likely to play a much more important role in cardiovascular physiology and pathology than was originally foreseen
Extensively illustrated with original diagrams and schematics that summarize the different steps of endothelium-dependent hyperpolarization, the text is designed for vascular biologists, and cardiologists, as well as graduate students looking to gain an understanding of the intimate functioning of the blood vessel wall.

The endothelium, a monolayer of endothelial cells, constitutes the inner cellular lining of the blood vessels (arteries, veins and capillaries) and the lymphatic system, and therefore is in direct contact with the blood/lymph and the circulating cells. The endothelium is a major player in the control of blood fluidity, platelet aggregation and vascular tone, a major actor in the regulation of immunology, inflammation and angiogenesis, and an important metabolizing and an endocrine organ. Endothelial cells controls vascular tone, and thereby blood flow, by synthesizing and releasing relaxing and contracting factors such as nitric oxide, metabolites of arachidonic acid via the cyclooxygenases, lipoxygenases and cytochrome P450 pathways, various peptides (endothelin, urotensin, CNP, adrenomedullin, etc.), adenosine, purines, reactive oxygen species and so on. Additionally, endothelial ectoenzymes are required steps in the generation of vasoactive hormones such as angiotensin II. An endothelial dysfunction linked to an imbalance in the synthesis and/or the release of these various endothelial factors may explain the initiation of cardiovascular pathologies (from hypertension to atherosclerosis) or their development and perpetuation. Table of Contents: Introduction / Multiple Functions of the Endothelial Cells / Calcium Signaling in Vascular Cells and Cell-to-Cell Communications / Endothelium-Dependent Regulation of Vascular Tone / Conclusion / References

The endothelium controls vascular tone by releasing various vasoactive substances. Additionally, another pathway associated with the hyperpolarization of both endothelial and vascular smooth muscle cells contributes also to endothelium-dependent relaxations (EDHF-mediated responses). These responses involve an increase in the intracellular Ca concentration of the endothelial cells followed by the opening of Ca-activated K channels of small and intermediate conductances (SKCa and IKCa). These channels show a distinct subcellular distribution, suggesting that their activation could be elicited by distinct stimuli. Following KCa activation, the endothelial hyperpolarization can be conducted to the underlying smooth muscle cells by electrical coupling through myo-endothelial gap junctions. In addition, the potassium efflux can lead to the accumulation of potassium ions in the intercellular space and the subsequent activation of smooth muscle Kir2.1 and/or Na/K-ATPase. The hyperpolarization of the smooth muscle cells produces vascular relaxation, predominantly by closing voltage-gated calcium channels, and vasodilatation. EDHFmediated responses are altered in various pathologies or, conversely, act as a compensating mechanism when other endothelial pathways are impaired. A better characterization of EDHF-mediated responses should allow determining whether or not new drugable targets can be identified within this endothelial pathway for the treatment of cardiovascular diseases. Table of Contents: Endothelium-Dependent Hyperpolarizations: The Classical "EDHF" Pathway / Conclusion / References