Increased ET-1 and Reduced ETB Receptor Expression in Uremic Hypertensive Rats

The endothelin-1 (ET-1) system has been implicated in cardiovascular disease associated with chronic renal failure. We investigated the expression and localization of ET-1 and the ETB and ETA receptors in vascular and renal tissues of uremic hypertensive rats. Uremia was induced by renal artery branches ligation. At week 6, blood and renal parameters, and plasma and urine ET-1 levels were evaluated. The ET-1, and the ETB and ETA receptors expression and localization were determined by Northern and Western blotting, and by immunofluorescence, respectively. Blood pressure, serum creatinine, proteinuria, and urinary ET-1 were increased in uremic rats. The ET-1 expression was increased in the aorta, mesenteric arteries, and the renal cortex of uremic rats, whereas the ETB receptor expression was reduced. Immunofluorescence analysis using the thoracic aorta revealed that the endothelial ET-1 levels were increased 4-fold in uremic rats. In contrast, the ETB receptor expression, which was localized exclusively in the endothelium, was markedly reduced. The ETA receptor expression, however, was increased 1.6-fold and was detected in the media only. Similar changes in ET-1 and ETB receptor expression were observed in renal cortex vessels and glomeruli of uremic rats. This study reveals that ET-1 levels are augmented in the vascular endothelium of uremic rats, whereas the ETB receptor expression is reduced which may play a major role in hypertension and renal failure progression.