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.
Table of Contents
THE BLOOD VESSEL WALL
Multiple Functions of the Endothelial Cells
Vascular Smooth Muscle
Membrane Potential and Calcium Homeostasis in Vascular Smooth
Muscle and Endothelial Cells
Metabolism of Arachidonic Acid
Nitric Oxide Synthases
The Other Endothelium-Derived Vasoactive Factors
The Third Pathway: Historical Notes
Endothelium-Dependent Hyperpolarizations: Involvement of Calcium-Activated Potassium Channels
Identification of the Potassium Channels Involved in EDHF-Mediated Responses
Endothelium-Dependent Hyperpolarization: Localization of the Potassium Channels
IKCa, SKCa, and Endothelial Hyperpolarization
Beyond Endothelial Hyperpolarization
EDHF-Mediated Responses in Human Blood Vessels
EDHF AND THE PHYSIOLOGICAL CONTROL OF BLOOD FLOW
NOS-3 Knock-Out Mice
EDHF and Arterial Blood Pressure
EDHF and Gender
EDHF AND ENDOTHELIAL DYSFUNCTION
Atherosclerosis and Hypercholesterolemia
EDHF AND THERAPEUTIC INTERVENTIONS
Angiotensin-Converting Enzyme Inhibitors and Antagonists of the AT1-Angiotensin Receptor (AT1)
Calcium Channel Blockers
ET-A Receptor Antagonists