Activation of RAAS in a rat model of liver cirrhosis: no effect of losartan on renal sodium excretion

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.

Fasting increases circulating angiotensin levels and brain Agtr1a expression in male rats

“…After food reintroduction, treatment with losartan in drinking water did not promote any differences in bodyweight gain, urinary volume, or sodium or potassium urinary excretion, confirming previous data using a similar dose 62 . As expected, food and water ingestion were greater in fasted animals.…”

“…After food reintroduction, treatment with losartan in drinking water did not promote any differences in bodyweight gain, urinary volume, or sodium or potassium urinary excretion, confirming previous data using a similar dose. 62 As expected, food and water ingestion were greater in fasted animals. Animals that were fasted and dosed with oral losartan showed reduced water intake in the first hour after chow was reintroduced, demonstrating a possible role of ANG II/AT 1 R signalling in thirst induced by renewed feeding in fasted rats.…”