Abstract
BackgroundLiver cirrhosis is characterized by avid sodium retention where the activation of the renin angiotensin aldosterone system (RAAS) is considered to be the hallmark of the sodium retaining mechanisms. The direct effect of angiotensin II (ANGII) on the AT-1 receptor in the proximal tubules is partly responsible for the sodium retention. The aim was to estimate the natriuretic and neurohumoral effects of an ANGII receptor antagonist (losartan) in the late phase of the disease in a rat model of liver cirrhosis.MethodsBile duct ligated (BDL) and sham operated rats received 2 weeks of treatment with losartan 4 mg/kg/day or placebo, given by gastric gavage 5 weeks after surgery. Daily sodium and potassium intakes and renal excretions were measured.ResultsThe renal sodium excretion decreased in the BDL animals and this was not affected by losartan treatment. At baseline the plasma renin concentration (PRC) was similar in sham and BDL animals, but increased urinary excretion of ANGII and an increase P-Aldosterone was observed in the placebo treated BDL animals. The PRC was more than 150 times higher in the losartan treated BDL animals (p < 0.001) which indicated hemodynamic impairment.ConclusionsLosartan 4 mg/kg/day did not increase renal sodium excretion in this model of liver cirrhosis, although the urinary ANGII excretion was increased. The BDL animals tolerated Losartan poorly, and the treatment induced a 150 times higher PRC.
Highlights
Liver cirrhosis is characterized by avid sodium retention where the activation of the renin angiotensin aldosterone system (RAAS) is considered to be the hallmark of the sodium retaining mechanisms
In the Bile duct ligated (BDL) losartan group 1 animal was found dead on day 6 due to intraperitoneal bleeding. 3 animals where terminated on day 5, 10 and 14 according to the rules of animal welfare
S-bilirubin and B-leucocytes were significantly higher in the BDL animals and S-albumin as well as the platelet count was lower compared to the sham controls
Summary
Liver cirrhosis is characterized by avid sodium retention where the activation of the renin angiotensin aldosterone system (RAAS) is considered to be the hallmark of the sodium retaining mechanisms. Impaired renal sodium handling is partly due to increased angiotensin II (ANGII) as well as aldosterone levels and its action at the proximal, distal and collecting tubules in the kidneys Both ANGII and aldosterone are expected to be increased in cirrhosis secondary to the central vasodilation, reduced effective blood volume, where the neurohumoral response maintain blood pressure [1]. Has to be explored, whether long-term treatment with ANGII receptor antagonists may improve sodium excretion in the late phase of the diseases where formation of ascites is frequent It is hypothesized, that long-term treatment with losartan increases sodium excretion in the BDL model of cirrhosis in the late course of disease by direct blockage of the AT1 receptor and reduction of aldosterone secretion
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