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

"What we call the beginning is often the end, and to make an end is to make a beginning. The end is where we start from." T. S. ELIOT, "Geroniton" The discovery of endothelin-l was both an end and a beginning. It is an end because this discovery has started a plethora of investigations as to endothe1in's sites of production, mode of action, it's normal and abnormal physiological role and its involvement in a variety of pathological conditions ranging from renal failure to myocardial infarction, cardiac hypertrophy, hyperten sion, cyclosporine induced toxicity, mental depression, renal failure, stress related illness, and even stroke and sudden death. It is a beginning because no one can foresee where the investigations will ultimately lead, or how they will end. The discovery of the endothelins was a very recent event and soon specialist books will start to appear dealing in detail with different aspects of their chemistry, physiological role and pathological importance. The present book is intended to act as a guide and primer for those who are becoming intrigued by the many endothelin related articles which are now appearing in the journals but who as yet have not had the time or opportunity to be caught up in the web of enthusiasm and excitement which is motivating those more directly involved in the field of research.

Peptides play a crucial role in many physiological processes including actions as neurotransmitters, hormones, and antibiotics. Research has shown their importance in such fields as neuroscience, immunology, pharmacology, and cell biology. The Handbook of Biologically Active Peptides presents, for the first time, this tremendous body of knowledge in the field of biologically active peptides in one single reference. The section editors and contributors represent some of the most sophisticated and distinguished scientists working in basic sciences and clinical medicine. The Handbook of Biologically Active Peptides is a definitive, all-encompassing reference that will be indispensable for individuals ranging from peptide researchers, to biochemists, cell and molecular biologists, neuroscientists, pharmacologists, and to endocrinologists. Chapters are designed to be a source for workers in the field and will enable researchers working in a specific area to examine other related areas with which they would not ordinarily be familiar.*Chapters are designed to be a source for workers in the field and will enable researchers working in a specific area to examine other related areas that they would not ordinarily be familiar.*Fascinating relationships described in the book include the presence of some peptides originally found in frog skin that persist in the human human and brain where they can affect food intake and obesity.

The biology of the family of endogenous autocrine peptides known as the endothelins (ETs) has been a source of intense study for researchers since 1988, following the identification of ET-l as the previously described endothelium-derived contractile factor. Initial interest focussed on the actions of the ETs in the cardiovascular system, and this remains the pri mary source of published work involving these peptides. Importantly, evi dence is mounting for a significant mediator role for ET-l in cardiovascu lar diseases including systemic hypertension and congestive heart failure. However, it was also recognized early on that the ETs exert an array of powerful actions in the respiratory tract, many of which prompted specula tion concerning mediator roles for ET-l in several lung diseases including asthma and pulmonary hypertension. In recent years the evidence for the involvement of ET-l in lung diseases has become more compelling. There is now real hope and anticipation that novel ET receptor antagonists may eventually be used therapeutically against asthma and other major lung pathologies. It is this atmosphere of excitement created by new discoveries and the increasing scientific ratio nale for a significant impact ofthe ETs in pulmonary diseases that prompt ed the creation of this book, the first on this topic. Most of the information presented relates to ET-l, which is the most widely studied member of the ET family.

Recent publications have addressed specific aspects of the endothelins, such as their roles in disease or the importance of endothelin receptors. However, in this book the entire field of endothelins is covered. This includes the pathways of endothelin production and their regulation, the local and systemic actions of endothelins, receptors for the endothelins and the signalling pathways employed, and the involvement of endothelins in a range of diseases. Attention is also paid to the development through chemistry, pharmacology and toxicology of endothelin antagonists and endothelin-converting enzyme inhibitors, with mention of all the important members of these drug classes. This leads to well-rounded discussions of the potential therapeutic benefit of endothelin inhibitors.

Endothelium and Cardiovascular Diseases: Vascular Biology and Clinical Syndromes provides an in-depth examination of the role of endothelium and endothelial dysfunction in normal vascular function, and in a broad spectrum of clinical syndromes, from atherosclerosis, to cognitive disturbances and eclampsia. The endothelium is a major participant in the pathophysiology of diseases, such as atherosclerosis, diabetes and hypertension, and these entities are responsible for the largest part of cardiovascular mortality and morbidly. Over the last decade major new discoveries and concepts involving the endothelium have come to light. This important reference collects this data in an easy to reference resource. Written by known experts, and covering all aspects of endothelial function in health and disease, this reference represents an assembly of recent knowledge that is essential to both basic investigators and clinicians. - Provides a complete overview of endothelial function in health and diseases, along with an assessment of new information - Includes coverage of groundbreaking areas, including the artificial LDL particle, the development of a new anti-erectile dysfunction agent, a vaccine for atherosclerosis, coronary calcification associated with red wine, and the interplay of endoplasmic reticulum/oxidative stress - Explores the genetic features of endothelium and the interaction between basic knowledge and clinical syndromes

Endothelin-1 (ET-1), a peptide discovered in 1988, is one of the most potent contractors of vascular smooth muscle. Since their discovery, ETs have generated enormous interest in the scientific and pharmaceutical communities, prompting extensive research. This book addresses the latest findings regarding ETs-how they function, their effects, and characteristics. Divided into five sections, the book covers: endothelin receptors, endothelin synthesis and degradation, endothelin pathophysiology, ligand structure and activity relationships, and clinical studies. Pharmacologists, toxicologists, and pharmaceutical researchers will all benefit from this thorough review of current findings and future directions in ET research.