The endothelin system in septic and endotoxin shock

The view of the endothelium as a passive barrier has gradually changed as a number of endothelium-derived substances have been discovered. Substances like nitric oxide, prostaglandins and endothelins have potent and important properties, involving not only the circulation as such but also the respon se to stimuli like inflammation and trauma. The endothelin system, discover ed in 1988, has not only strong vasoconstrictor properties, but also immuno modulating, endocrinological and neurological effects exerted through at le ast two types of receptors. Septic shuck, a condition with high mortality, is associated with vast cardiovascular changes, organ dysfunction with micr ocirculatory disturbances and dysoxia. In the experimental setting, endotox aemia resembles these changes and is, as well as septic shock, accompanied by a pronounced increase in plasma endothelin levels. The pathophysiology i n septic and endotoxin shock remains to be Fully elucidated, but several st udies indicate that endothelial dysfunction is one contributing mechanism. Activation of the endothelin system is associated with several pathological conditions complicating septic shock, such as acute respiratory distress s yndrome, cardiac dysfunction, splanchnic hypoperfusion and disseminated int ravascular coagulation. Through the development of both selective and nonse lective endothelin receptor antagonists, the endothelin system has been the object of a large number of studies during the last decade. This review hi ghlights systematically the findings of previous studies in the area. It pr ovides strong indications that the endothelin system, apart from being a ma rker of vascular injury, is directly involved in the pathophysiology of sep tic and endotoxin shock. Interventions with endothelin receptor antagonists during septic and endotoxin shock have so far only been done in animal stu dies but the results are interesting and promising. (C) 2000 Elsevier Scien ce B.V. All rights reserved.