Renal Endothelin System in Rats with Liver Cirrhosis

Abstract

Rats with experimental liver cirrhosis have increased endothelin-1 (ET-1) plasma concentrations and show a tendency toward sodium and water retention. We therefore analyzed the renal ET system in cirrhotic rats and control rats, as the renal ET system is involved in the regulation of water and sodium excretion. Cirrhosis was induced by carbon tetrachloride (CCl4) administration. We analyzed the expression of ET receptor subtypes in the renal cortex and medulla using Scatchard analysis and receptor autoradiography, and measured plasma and renal tissue ET-1 concentrations using a specific radioimmunoassay. Furthermore, we analyzed the effects of the nonselective (A/B) ET receptor antagonist bosentan on water and sodium excretion and glomerular filtration rate. Our study revealed an overexpression of the ETB receptor in the renal medulla of rats with liver cirrhosis, whereas the density of ETB receptor in the cortex and the ETA receptor in the cortex and medulla were similar in both cirrhotic and control rats. Receptor autoradiography showed that the upregulation of medullary ETB in cirrhotic rats was due to an upregulation of ETB in the inner medullary collecting duct cells. The highest ET-1 concentrations were observed in the renal medulla of cirrhotic rats. Glomerular filtration rate decreased in cirrhotic rats but was not altered after bosentan treatment in cirrhotic and control rats. Bosentan decreased sodium excretion in both cirrhotic and control rats to a similar extent, whereas water excretion was reduced by bosentan only in cirrhotic rats. We therefore suggest that the upregulation of medullary ETB in cirrhotic rats is involved int he regulation of water excretion in rats with CCl4-induced cirrhosis.