Endothelin and Its Inhibitors

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.

1 Historical Perspective and Introduction to the Endothelin Family of Peptides.- 2 Sarafotoxins and Their Relationship to the Endothelin Family of Peptides.- 3 Identity of Endothelin-Converting Enzyme and Other Targets for the Therapeutic Regulation of Endothelin Biosynthesis.- 4 Endothelin Receptors.- 5 Cell Signaling by Endothelin Peptides.- 6 Lessons from Gene Deletion of Endothelin Systems.- 7 Endothelin-Converting Enzyme Inhibitors and their Effects.- 8 Endothelin Converting Enzymes and Endothelin Receptor Localisation in Human Tissues.- 9 Endothelin Receptor Antagonists.- 10 Toxicology of Endothelin Antagonists.- 11 Endothelins and the Release of Autacoids.- 12 The Roles of Endothelins in Proliferation, Apoptosis, and Angiogenesis.- 13 The Involvement of Endothelins in Cerebral Vasospasm and Stroke.- 14 Involvement of the Endothelins in Airway Reactivity and Disease.- 15 Endothelin-1 and Pulmonary Hypertension.- 16 Vascular and Cardiac Effects of Endothelin.- 17 Endothelins Within the Liver and the Gastrointestinal System.- 18 Endothelin and the Kidney.- 19 Endothelin Ligands and their Experimental Effects Within the Human Circulation.