Collecting duct function in liver cirrhotic rats with early sodium retention

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Liver cirrhosis is a chronic disease associated with sodium retention due to increased tubular sodium reabsorption. However, the exact tubular site of increased sodium reabsorption in uncertain. We have recently demonstrated selective hypertrophy of the inner stripe of the outer medulla (ISOM) in rats with liver cirrhosis induced by common bile duct ligation (CBL). The present study was designed in order to measure Na–K–ATPase activity in the two major tubular segments located in the ISOM: the thick ascending limb of henles (MTAL) and the collecting ducts (OMCD) in CBL rats. Sham-operated rats were used as controls. In addition, the natriuretic response to amiloride (0.2 mg kg−1 h−1 i.v) was examined in conscious, chronically instrumented rats during conditions where amiloride-induced volume losses were replaced continuously using a servo-controlled i.v. volume replacement system. For 4–5 weeks after CBL, cirrhotic rats showed sodium retention relative to control rats without any sign of ascites. Plasma levels of sodium and aldosterone were normal, but plasma vasopressin was increased. Effective renal plasma flow was significantly increased, whereas glomerular filtration rate (GFR) and renal lithium handling were normal. The CBL rats showed a blunted natriuretic response to amiloride (ΔFENa: 1.17 ± 0.15% vs. 1.65 ± 0.13%; P < 0.05). In rats with CBL, Na–K–ATPase activity per mm tubular length was decreased in the OMCD and unchanged in the TAL segment. These results suggest that increased tubular sodium reabsorption in liver cirrhotic rats with early sodium retention is localized in segments proximal to the collecting ducts.

Keywords: Na–K–ATPase; amiloride; cirrhosis; collecting duct; sodium retention

Document Type: Research Article


Affiliations: Department of Pharmacology, The Panum Institute, University of Copenhagen, DK-2200 Copenhagen N, Denmark

Publication date: July 1, 2002

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