Endothelin in unilateral ureteral obstruction: vascular and cellular effects

PURPOSE: Unilateral ureteral obstruction results in decreased blood flow and tissue loss in the obstructed kidney. This condition is compensated by increased perfusion and trophic changes in the contralateral kidney. Vascular mediators' effects are central to these changes and of these mediators endothelin is the most potent vasoconstrictor known. We explored the role of endothelin and the effects of endothelin receptor blockade in unilateral ureteral obstruction. MATERIALS AND METHODS: Rats were subjected to unilateral ureteral obstruction for 24 hours. Endothelin-1 mRNA expression was determined in kidney extracts from control, obstructed and contralateral (nonobstructed) kidneys. Cortical and medullary blood flow was determined in control and obstructed kidneys, and after endothelin receptor blockade with bosentan. Apoptotic rates were determined in control and obstructed kidneys after treatment with bosentan using the terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end technique.RESULTS After 24 hours of unilateral ureteral obstruction endothelin-1 mRNA expression was increased in the obstructed kidney and decreased in the contralateral kidney. Obstruction was associated with a decrease in renal blood flow, which was reversed by endothelin receptor blockade. Unilateral ureteral obstruction also increased apoptosis, which was blocked by endothelin inhibition. CONCLUSIONS: Endothelin expression increases in the obstructed kidney. Inhibition of its action protects against vascular and cellular changes. Decreased endothelin expression in the contralateral kidney may facilitate trophic changes and compensatory increased blood flow.