Pathophysiological role of endothelin in acute renal failure

In conscious rats, the i.v. injection of endothelin (ET) caused an increase in blood urea nitrogen (BUN), an index of renal dysfunction. In the model of acute renal failure which was induced by occlusion of the bilateral renal arteries of rats followed by reperfusion, ET-monoclonal antibody improved the renal function. In this model, ET-antibody also protected the kidneys from renal proximal tubular necrosis and suppressed Ca++-accumulation in necrotic tissues. Plasma ET level increased 5 min and 5 hr and renal ET content did 5 and 20 hr after reperfusion. BUN level increased 5 and 20 hr after reperfusion. These results strongly suggest that the endogenously increased ET may be one of the important deleterious mediators in the pathogenesis of ischemic acute renal failure.