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

Abstract

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 ET_B and ET_A 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 ET_B and ET_A 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 ET_B 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 ET_B receptor expression, which was localized exclusively in the endothelium, was markedly reduced. The ET_A receptor expression, however, was increased 1.6-fold and was detected in the media only. Similar changes in ET-1 and ET_B 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 ET_B receptor expression is reduced which may play a major role in hypertension and renal failure progression.

Keywords:

• endothelin-1
• ET_B receptor
• renal failure
• hypertension
• endothelium
• immunofluorescence

ACKNOWLEDGMENTS

The authors thank Danielle Lizotte and Claude Villeneuve for their technical assistance. This study was supported by grants from the Kidney Foundation of Canada and the Canadian Institutes of Health Research (MOP-57683) to RL. RL is a recipient of a research scholarship from the Fonds de la Recherche en Santé du Québec and MD holds a studentship from the Canadian Institutes of Health Research.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.