Portal Pressure Response To Losartan Compared With Propranolol in Patients With Cirrhosis

De, Binay K; Bandyopadhyay, Kausik; Das, Tapas; Das, Debasish; Biswas, Pranab Kumar; Majumdar, Debabrata; Mandal, S. K.; Ray, Sujay; Dasgupta, Shyamal

doi:10.1111/j.1572-0241.2003.07497.x

Cited by 58 publications

(39 citation statements)

References 31 publications

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“…For example, fibrosis in liver, kidney, lung, and heart have been linked to AngII activity in experimental animal models. [3][4][5] In humans, it has been shown that losartan, an angiotensin II type 1 (AT1) receptor antagonist, not only decreases portal pressure in cirrhosis, 6 but also may have antifibrotic effects in liver. 7 Therefore, the RAS seems to play key roles in tissue remodeling and scarring, especially after injury.…”

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confidence: 99%

Role of the renin-angiotensin system in hepatic ischemia reperfusion injury in rats

et al. 2004

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It has been shown that the renin-angiotensin system (RAS) plays key roles in the development of fibrosis in numerous organs, including the liver. Other studies have suggested that the RAS also may play roles in diseases of chronic inflammation. However, whether the RAS also can mediate acute inflammation in liver is unclear. The purpose of this study therefore was to determine the effect of the RAS inhibitors captopril and losartan on acute liver damage and inflammation caused by hepatic ischemia and subsequent reperfusion. Accordingly, male rats were subjected to 1 hour of hepatic ischemia (70%) followed by reperfusion; animals were killed 3, 8, or 24 hours after reperfusion. The effect of captopril or losartan (100 or 5 mg/kg intragastrically, respectively) was compared with that of vehicle (saline). The expression of angiotensinogen in liver increased fivefold 3 hours after reperfusion. Indices of liver damage and inflammation (e.g., alanine aminotransferase levels, pathological features, tumor necrosis factor-␣ levels, and intercellular adhesion molecule-1 expression) all were significantly elevated in vehicle-treated animals after hepatic ischemia and subsequent reperfusion. Ischemia and reperfusion also caused an increase in the accumulation of protein adducts of 4-hydroxynonenal, an index of oxidative stress. Captopril or losartan treatment showed profound protective effects under these conditions, significantly blunting the increase in all these parameters caused by ischemia and reperfusion. In conclusion, RAS inhibitors prevent acute liver injury in a model of inflammation caused by ischemia and reperfusion. These data further suggest that the RAS may play a key role in mediating such responses in the liver and suggest a novel role for this system. (HEPATOLOGY 2004;40:583-589.)

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confidence: 99%

Role of the renin-angiotensin system in hepatic ischemia reperfusion injury in rats

et al. 2004

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“…In addition, Lay et al 18 documented that 16% of patients had to withdraw from the propranolol therapy due to adverse events such as hypotension and dizziness. However, in other literatures, 6,10 no adverse effects were observed throughout the study. In the present study, the only complication noted was dizziness: this was found in 24% of the patients treated with propranolol.…”

Section: Discussionmentioning

confidence: 61%

Effect of Propranolol on Portal Pressure and Systemic Hemodynamics in Patients with Liver Cirrhosis and Portal Hypertension: A Prospective Study

Suk¹,

Kim²,

Park³

et al. 2007

Gut Liver

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Background/Aims: Propranolol can prevent variceal bleeding by ameliorating portal hypertension. We conducted this study to determine the effect of propranolol on portal hypertension and the optimal required dose in Korean cirrhotic patients. Methods: This study prospectively evaluated 50 patients with cirrhosis who exhibited variceal bleeding. The hepatic venous pressure gradient (HVPG), portal venous flow, heart rate (HR), and blood pressure were assessed both at baseline and at 3 months after the treatment. The initial dose of propranolol (20 mg) was subsequently adjusted until the target HR was reached. Patients in whom HVPG reduced by ＞20% or to less than 12 mmHg were defined as responders. Results: Propranolol significantly (p＜0.01) reduced the HVPG ( 21±26%, mean±standard deviation), portal venous flow ( 25±21%), HR ( 20±13%), and blood pressure ( 3±13%). Twenty-nine patients were responders, and the optimal required dose was 154.4 mg. The main complication was dizziness (24%), but this was not serious enough to require medication withdrawal. Conclusions: Propranolol is safe and effective at reducing portal pressure in Korean cirrhotic patients. An effective improvement in portal hypertension requires the dose to be increased until the target HR is reached. (Gut and Liver 2007;1:159-164)

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“…Von Bergmann et al reported that after once-daily oral doses of 10 mg olmesartan were given to patients with mild and moderate hepatic impairment (Child-Pugh scores of B6 and 7-9, respectively), the daily maximum concentration of the drug in the body was generally similar to that in healthy matched subjects, but the area under the curve increased by 30 and 48%, respectively, and was reflected in increases of absolute bioavailability values compared with those in healthy subjects [23]. De et al [24] showed that low-dose losartan was as effective as propranolol in reducing portal pressure in cirrhotic patients. On the other hand, Schepke et al [25] showed that another ARB, irbesartan, moderately reduced portal pressure but induced marked arterial hypotension and renal impairment in patients with advanced cirrhosis.…”

Section: Discussionmentioning

confidence: 96%

Effects of 1-year administration of olmesartan on portal pressure and TGF-beta1 in selected patients with cirrhosis: a randomized controlled trial

et al. 2011

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Portal Pressure Response To Losartan Compared With Propranolol in Patients With Cirrhosis

Cited by 58 publications

References 31 publications

Role of the renin-angiotensin system in hepatic ischemia reperfusion injury in rats

Role of the renin-angiotensin system in hepatic ischemia reperfusion injury in rats

Effect of Propranolol on Portal Pressure and Systemic Hemodynamics in Patients with Liver Cirrhosis and Portal Hypertension: A Prospective Study

Effects of 1-year administration of olmesartan on portal pressure and TGF-beta1 in selected patients with cirrhosis: a randomized controlled trial

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