In a variety of pathological states, notably ischaemia–reperfusion injury, organ infarction, and shock, there are substantial increases in the normally low circulating concentrations of endothelin-1 (ET-1).1 ,2 This is more than just a symptom. ET-1 seems to be an active participant in these disorders as antibodies directed against ET-1 and endothelin receptor antagonists are protective.1 ,2 Interestingly, although studies in isolated cells suggest that the production of ET-1 can only be up-regulated over the course of hours, increases in vivo can be recorded within much shorter periods. For example, intravenous injection of a high dose of endotoxin to anaesthetised rats causes within 5–10 minutes both a dramatic fall in blood pressure and a notable increase in haematocrit. Both of these effects are greatly reduced by treatment …