Liver Cirrhosis Research Today is a free monthly online journal that collates and summarizes the latest research about Liver Cirrhosis, including details on alcohol, treatment, drugs, effects, causes.

Vascular, hemodynamic and renal effects of low-dose losartan in rats with secondary biliary cirrhosis.

Heller J, Trebicka J, Shiozawa T, Schepke M, Neef M, Hennenberg M, Sauerbruch T

Department of Internal Medicine I, University of Bonn, Bonn, Germany. jheller@uni-bonn.de

BACKGROUND: In cirrhosis, splanchnic and systemic vasodilatation induce a hyperdynamic circulatory dysfunction, portal hypertension and renal sodium retention. This vasodilatation is in part because of an impaired vascular response to alpha1-adrenoceptor agonists. Recently, the angiotensin II type 1-receptor antagonist losartan has been shown to attenuate portal hypertension. We hypothesized that losartan decreases portal pressure by counteracting the impaired vascular responsive to alpha1-adrenoceptor agonists. METHODS: We studied, in rats with secondary biliary cirrhosis and sham-operated rats, the effect of 0.5 and 10 mg losartan/kg x day on aortic responsiveness to alpha1-adrenoceptor stimulation with methoxamine and angiotensin II (myograph), splanchnic and systemic hemodynamics (colored microspheres), plasma noradrenaline levels and kidney function. RESULTS: In cirrhotic rats, 10 mg losartan/kg x day completely inhibited aortic contractility to angiotensin II, decreased vascular resistance and arterial pressure and induced renal failure. In contrast, 0.5 mg losartan/kg x day only partially inhibited aortic contractility to angiotensin II, but improved aortic contractility to methoxamine, increased splanchnic and systemic vascular resistance, decreased portal pressure, decreased plasma norepinephrine levels and induced natriuresis. CONCLUSIONS: In cirrhotic rats, losartan at a very low dose increases splanchnic vascular resistance, decreases portal pressure and improves kidney function, possibly by an increased vascular responsiveness to alpha1-adrenoceptor agonists.

Published 24 May 2005 in Liver Int, 25(3): 657-66.
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