ON THE HORIZON
2-18 THE ENDOTHELIN SYSTEM IN CARDIOVASCULAR DISEASE
The function of vascular endothelium has become a major focus of research. This is partly due to the success of drugs (angiotensin converting enzyme inhibitors, nitro-vaso dilators, and aspirin) which act through mechanisms related to endothelial function. Endothelial dysfunction is now thought to be an important early factor predisposing to atherogenesis.
Endothelin-1 is a recently discovered endothelium-derived vasoconstrictor and pressor peptide. It influences basal vascular tone and blood pressure. The vasoconstriction caused by endothelin-1 is modulated by nitric oxide (NO) and prostacyclin. The generation of endothelin-1 is increased by a wide range of vasoactive and inflammatory mediators, changes in sheer stress of the vessel wall, and hypoxia. There is evidence that endothelin-1 plays a role in local ischemia (including myocardial infarction), vasospasm (including Raynaud’s disease and subarachnoid hemorrhage), and sustained vasoconstriction (including hypertension and heart failure).
The role of endothelin-1 in heart failure (HF) has attracted the most interest. Neurohumoral activation and tissue hypoxia should also increase production of endothelin-1, leading to vasoconstriction, enhanced activity of the renin-angiotensin system and the sympathetic nervous system, increased renal vasoconstriction, and sodium retention.
Antagonists to endothelin are currently under development and may provide an important new approach to the treatment of cardiovascular disease. Early clinical studies have shown encouraging benefits in treatment of chronic heart failure.
BMJ February 22, 1997; 314: 531 Editorial from Western General Hospital, Edinburgh, UK

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