BACKGROUND/AIMS: Nitric oxide and angiotensin play important roles in the pathogenesis of the hemodynamic derangement in cirrhosis and portal hypertension. The hemodynamic effects of losartan, an angiotensin II type 1 receptor antagonist, in cirrhotic patients with portal hypertension are conflicting. This study was undertaken to explore the possible mechanism of action of losartan on portal hypertension in cirrhotic rats produced by bile duct ligation (CBL). METHODS: Three weeks after surgery, CBL and sham-operated rats randomly received vehicle or losartan (3 mg/kg per 12 h by gavage) for 1 week. Hemodynamic values, hormone levels, and aortic eNOS protein expression were measured after drug administration. RESULTS: In CBL rats, 1-week losartan treatment decreased portal pressure and ameliorated hyperdynamic circulation associated with a blunted vascular response to N(omega)-nitro-L-arginine methyl ester infusion. The hematocrit increased and the plasma volume, aldosterone, plasma renin activity, norepinephrine, and nitrate and nitrite levels decreased. The eNOS protein expression was reduced in CBL rats receiving losartan compared with those receiving vehicle. CONCLUSIONS: One-week losartan treatment in CBL rats decreased portal pressure and ameliorated hyperdynamic circulation. In addition to the suppression of renin-angiotensin axis, the reduced aortic eNOS protein expression may play a partial role for the mechanism of action of losartan in CBL rats.
BACKGROUND/AIMS: Nitric oxide and angiotensin play important roles in the pathogenesis of the hemodynamic derangement in cirrhosis and portal hypertension. The hemodynamic effects of losartan, an angiotensin II type 1 receptor antagonist, in cirrhotic patients with portal hypertension are conflicting. This study was undertaken to explore the possible mechanism of action of losartan on portal hypertension in cirrhotic rats produced by bile duct ligation (CBL). METHODS: Three weeks after surgery, CBL and sham-operated rats randomly received vehicle or losartan (3 mg/kg per 12 h by gavage) for 1 week. Hemodynamic values, hormone levels, and aortic eNOS protein expression were measured after drug administration. RESULTS: In CBLrats, 1-week losartan treatment decreased portal pressure and ameliorated hyperdynamic circulation associated with a blunted vascular response to N(omega)-nitro-L-arginine methyl ester infusion. The hematocrit increased and the plasma volume, aldosterone, plasma renin activity, norepinephrine, and nitrate and nitrite levels decreased. The eNOS protein expression was reduced in CBLrats receiving losartan compared with those receiving vehicle. CONCLUSIONS: One-week losartan treatment in CBLrats decreased portal pressure and ameliorated hyperdynamic circulation. In addition to the suppression of renin-angiotensin axis, the reduced aortic eNOS protein expression may play a partial role for the mechanism of action of losartan in CBLrats.
Authors: Chandana B Herath; John S Lubel; Zhiyuan Jia; Elena Velkoska; David Casley; Lindsay Brown; Chris Tikellis; Louise M Burrell; Peter W Angus Journal: Am J Physiol Gastrointest Liver Physiol Date: 2009-04-23 Impact factor: 4.052
Authors: Joseph D Walch; T Prashant Nedungadi; J Thomas Cunningham Journal: Am J Physiol Regul Integr Comp Physiol Date: 2014-07-09 Impact factor: 3.619
Authors: Heder F G Estrela; Elaine S Damásio; Eduardo K U N Fonseca; Cássia T Bergamaschi; Ruy R Campos Journal: PLoS One Date: 2016-04-07 Impact factor: 3.240